Cancer treatments such as surgery and chemotherapy have several limitations, including ineffectiveness against large or persistent tumors, high relapse rates, drug toxicity, and non-specificity of therapy. Researchers are exploring advanced strategies for treating this life-threatening disease to address these challenges. One promising approach is targeted drug delivery using prodrugs or surface modification with receptor-specific moieties for active or passive targeting. While various drug delivery systems have shown potential for reaching hepatic cells, nano-carriers offer significant size, distribution, and targetability advantages. Engineered nanocarriers can be customized to achieve effective and safe targeting of tumors by manipulating physical characteristics such as particle size or attaching receptor-specific ligands. This method is particularly advantageous in treating liver cancer by targeting specific hepatocyte receptors and enzymatic pathways for both passive and active therapeutic strategies. It highlights the epidemiology of liver cancer and provides an in-depth analysis of the various targeting approaches, including prodrugs, liposomes, magneto-liposomes, micelles, glycol-dendrimers, magnetic nanoparticles, chylomicron-based emulsion, and quantum dots surface modification with receptor-specific moieties. The insights from this review can be immensely significant for preclinical and clinical researchers working towards developing effective treatments for liver cancer. By utilizing these novel strategies, we can overcome the limitations of conventional therapies and offer better outcomes for liver cancer patients.

Microbial resistance (MR) and cancer are global healthcare pitfalls that have caused millions of deaths and pose a significant pharmaceutical challenge, with clinical cases increasing. Thioureas are preferred structures in medicinal chemistry, chemosensors, and organic synthesis platforms. In fact, thiourea (TU) moieties serve as a common framework for several medications and bioactive substances, demonstrating a wide range of therapeutic and pharmacological accomplishments. The integration of the thiourea moiety into a diverse range of organic molecules has resulted in very flexible compounds with widespread uses in medicinal chemistry. Moreover, for over a century, TU and its metal complexes have been characterized for their biological activity. Finally, we provide an assessment and future outlook of different organo-thiourea derivatives, from the very beginning to the most recent discoveries in medicinal activity.

Breast cancer therapy can be improved by the application of multifunctional peptides and they have unique features, such as high specificity, minimized toxicity, and the capability to influence diverse processes. The role of peptides in breas cancer therapy is highlighted in the present review, examining their functions as therapeutic agents, diagnostic tools, and drug delivery application. Therapeutic peptides have displayed the ability to regulate key pathways in breast tumor, including HER2, VEGF, and EGFR, providing ideal alternatives to the conventional chemotherapy with reduced adverse effects. Additionally, peptide-based vaccines and immune-modulating peptides have demonstrated the capacity in enhancing anti-cancer immunity. The incorporation of peptides into nanoparticles has improved the delivery of drugs and genes, enhanced anti-cancer efficacy while minimizing side impacts. The progresses in the peptide engineering, including stapled peptides, peptide-drug conjugates, and cell-penetrating peptides, have remarkably increased their therapeutic efficacy and stability, elevating their applications in breast cancer therapy. Peptides can be developed using bioinformatics and high-throughput screening technologies to optimize pharmacokinetics and bioavailability. Despite their promise, peptides demonstrate challenges such as enzymatic degradation, limited stability, and high production costs. These obstacles can be addressed through strategies such as peptide cyclization, the employement of non-natural amino acids, and nanoparticle encapsulation. This review explores these recent advancements and strategies, providing ideal insights into the clinical potential of peptides in breast tumor therapy.

The side effects of chemotherapy drugs have prompted the development of targeted therapies. Distinctive abundance of lipid peroxidation (LPO) in tumour cells represents a potential target for drug delivery. However, LPO-based targeted ligands remain under-exploited. In this work, the targeting of 2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPO), was investigated within a mesoporous silica nanoparticle (MSN) loaded with doxorubicin (DOX) and connected with 4-NH2-TEMPO obtaining DOX/MSN-TEMPO. A cellular uptake assay showed a faster uptake of DOX/MSN-TEMPO than blank group on Hela, L929 and 4T1 cells, revealing TEMPO's active targeting ability for tumour cells. After observing this phenomenon, the fabrication of a basic copolymer module carrying cyanine5.5 (Cy5.5) and TEMPO was reported. In vivo experiments were conducted on mouse MCF-7 tumour models, displaying selective aggregation of nano micelles at the tumour site and thereby verifying the broad applicability of TEMPO. Since the large amounts of LPO lead to the presence of numerous free radicals, whereas TEMPO, as a free radical capture agent, further selectively targets tumour cells. These findings verify the targeting ability of TEMPO for most tumour cells and collectively underscore the potential of TEMPO and analogous capture agents as innovative targeted ligands for drug delivery.

Nanotechnology involves the utilization of materials with exceptional properties at the nanoscale. Over the past few years, nanotechnologies have demonstrated significant potential in improving human health, particularly in medical treatments. The self-assembly characteristic of RNA is a highly effective method for designing and constructing nanostructures using a combination of biological, chemical, and physical techniques from different fields. There is great potential for the application of RNA nanotechnology in therapeutics. This review explores various nano-based drug delivery systems and their unique features through the impressive progress of the RNA field and their significant therapeutic promises due to their unique performance in the COVID-19 pandemic. However, a significant hurdle in fully harnessing the power of RNA drugs lies in effectively delivering RNA to precise organs and tissues, a critical factor for achieving therapeutic effectiveness, minimizing side effects, and optimizing treatment outcomes. There have been many efforts to pursue targeting, but the clinical translation of RNA drugs has been hindered by the lack of clear guidelines and shared understanding. A comprehensive understanding of various principles is essential to develop vaccines using nucleic acids and nanomedicine successfully. These include mechanisms of immune responses, functions of nucleic acids, nanotechnology, and vaccinations. Regarding this matter, the aim of this review is to revisit the fundamental principles of the immune system's function, vaccination, nanotechnology, and drug delivery in relation to the creation and manufacturing of vaccines utilizing nanotechnology and nucleic acids. RNA drugs have demonstrated significant potential in treating a wide range of diseases in both clinical and preclinical research. One of the reasons is their capacity to regulate gene expression and manage protein production efficiently. Different methods, like modifying chemicals, connecting ligands, and utilizing nanotechnology, have been essential in enabling the effective use of RNA-based treatments in medical environments. The article reviews stimuli-responsive nanotechnologies for RNA delivery and their potential in RNA medicines. It emphasizes the notable benefits of these technologies in improving the effectiveness of RNA and targeting specific cells and organs. This review offers a comprehensive analysis of different RNA drugs and how they work to produce therapeutic benefits. Recent progress in using RNA-based drugs, especially mRNA treatments, has shown that targeted delivery methods work well in medical treatments.

Dendrimers are branched macromolecular structures that are useful nanocarriers for small-molecule drugs, such as cancer therapeutics. Their small size permits penetration into solid tumors, coupled with functionalization with a low-fouling PEG coating that minimizes transient cellular interactions and enhances plasma circulation time. While PEGylated dendrimers show significant promise as anticancer therapeutics, there is potential to increase tumor cell specificity and drive uptake of drugs into cells by conjugating cell-targeting ligands onto the dendrimers. To achieve this, we used an expanded genetic code and bio-orthogonal click chemistry to functionalize monomethyl auristatin E (MMAE)-loaded PEGylated dendrimers with a single tumor cell-targeting nanobody per dendrimer. The uniform addition of a single nanobody ligand facilitated greater intracellular uptake of the drug payload into HER2-positive target cells, while preserving the desirable circulatory characteristics of dendrimers. While the nanobody-dendrimer conjugates show similar levels of tumor infiltration over 24 h compared to unmodified dendrimers, the targeted dendrimers had significantly greater inhibition of tumor growth and long-term retention in the tumors. Our results highlight that biodistribution studies alone are poor predictors of therapeutic performance. The controlled conjugation strategy presented here preserves the size advantage and tissue penetration of dendrimers while maximizing targeted cellular uptake and potency in difficult-to-access solid tumor tissue.

New modes of targeted drug delivery are emerging with promise of enhancing therapeutic efficacy while reducing side effects. This review examines the landscape of metabolic glycan labelling-a technique gaining traction for its potential in specific drug targeting. By exploiting the natural glycan synthetic pathway of monosaccharides, unnatural sugar analogues are incorporated into glycoproteins, allowing for the presentation of unique functional groups on cells. This enables specific targeting using 'clickable' probes with complementary click chemistry functional groups. The selection of sugar analogues and chemical tags are crucial components explored in this review, alongside considerations for cell lines, tissues, and cargo selection. The review discusses non-therapeutic and therapeutic applications of metabolic glycan labelling, as well as its potential beyond labelling of cell surfaces. The review also highlights underexplored areas of metabolic glycan labelling by assessing the limited literature addressing labelling efficiency, turnover rates, the impact of sugar supplements in cell culture, and the critical cell to functionalised sugar ratio. Furthermore, this review delves into the future landscape and goals of metabolic glycan labelling, envisioning its potential in targeted drug delivery.

The multifaceted biological defense system modulating complex immune responses against pathogens and foreign materials plays a critical role in tissue homeostasis and disease progression. Recently developed biomaterials that can specifically regulate immune responses, nanoparticles, graphene, and functional hydrogels have contributed to the advancement of tissue engineering as well as disease treatment. The interaction between innate and adaptive immunity, collectively determining immune responses, can be regulated by mechanobiological recognition and adaptation of immune cells to the extracellular microenvironment. Therefore, applying immunomodulation to tissue regeneration and cancer therapy involves manipulating the properties of biomaterials by tailoring their composition in the context of the immune system. This review provides a comprehensive overview of how the physicochemical attributes of biomaterials determine immune responses, focusing on the physical properties that influence innate and adaptive immunity. This review also underscores the critical aspect of biomaterial-based immune engineering for the development of novel therapeutics and emphasizes the importance of understanding the biomaterials-mediated immunological mechanisms and their role in modulating the immune system.

Liposomal nanomedicines have emerged as a pivotal approach for the treatment of various diseases, notably cancer and infectious diseases. This manuscript provides an in-depth review of recent advancements in liposomal formulations, highlighting their composition, targeted delivery strategies, and mechanisms of action. We explore the evolution of liposomal products currently in clinical trials, emphasizing their potential in addressing diverse medical challenges. The integration of immunotherapeutic agents within liposomes marks a paradigm shift, enabling the design of 'immuno-modulatory hubs' capable of orchestrating precise immune responses while facilitating theranostic applications. The recent COVID-19 pandemic has accelerated research in liposomal-based vaccines and antiviral therapies, underscoring the need for improved delivery mechanisms to overcome challenges like rapid clearance and organ toxicity. Furthermore, we discuss the potential of "smart" liposomes, which can respond to specific disease microenvironments, enhancing treatment efficacy and precision. The integration of artificial intelligence and machine learning in optimizing liposomal designs promises to revolutionize personalized medicine, paving the way for innovative strategies in disease detection and therapeutic interventions. This comprehensive review underscores the significance of ongoing research in liposomal technologies, with implications for future clinical applications and enhanced patient outcomes.

The third most prevalent type of cancer in the world, colorectal cancer, poses a significant treatment challenge due to the nonspecific distribution, low efficacy, and high systemic toxicity associated with chemotherapy. To overcome these limitations, a targeted drug delivery system with a high cytotoxicity against cancer cells while maintaining a minimal systemic side effects represents a promising therapeutic approach. Therefore, the aim of this study was to develop an efficient gold nanocarrier for the targeted delivery of the anticancer agent everolimus to Caco-2 cells. A novel gold nanocomposite (EV-β-CD-HA-Chi-AuNCs) functionalized with a targeting ligand (hyaluronic acid), a permeation enhancement excipient (chitosan), and an anticancer inclusive compound consisting of beta-cyclodextrin and everolimus was proposed and prepared via Turkevich method. Characterization was performed with a UV spectrometer, FTIR, Zetasizer, and HRTEM. Its drug release profile was also evaluated in media with three different pH values. Cytotoxicity and biocompatibility studies were performed on a colorectal cancer cell line (Caco-2) and a normal fibroblast line (MRC-5), respectively, via xCELLigence real-time cellular analysis (RTCA) technology. The inhibitory effect on migration was also further tested via the xCELLigence RTCA technique and a scratch assay. Characterization studies revealed the successful formation of EV-β-CD-HA-Chi-AuNCs with a size and charge which are suitable for the use as targeted drug delivery carrier. In the cytotoxic study, the EV-β-CD-HA-Chi-AuNCs showed a lower IC50 (16 ± 1 µg/ml) than the pure drug (25 ± 3 µg/ml) toward a colorectal cell line (Caco-2). In the biocompatibility study, the EV-β-CD-HA-Chi-AuNCs have minimal toxicity, while the pure drug has severe toxicity toward healthy fibroblasts (MRC-5) despite its low concentration. In the cell migration study, the EV-β-CD-HA-Chi-AuNCs also showed a greater inhibitory effect than the pure drug. Compared with the pure drug, the EV-β-CD-HA-Chi-AuNCs exhibit an excellent selective cytotoxicity between cancerous colorectal Caco-2 cells and healthy MRC-5 cells, making it a potential carrier to carry the drug to the cancerous site while maintaining its low toxicity to the surrounding environment. In addition, an increase in the cytotoxic activity of the EV-β-CD-HA-Chi-AuNCs toward cancerous colorectal Caco-2 cells was also observed, which can potentially improve the treatment of colorectal cancer.

Surgery and chemoradiotherapy are the main clinical treatment methods for colorectal cancer (CRC), but the prognosis is poor. The emergence of nanomedicine brings bright light to the treatment of CRC. However, there has not been a comprehensive and systematic analysis of CRC and nanomedicine by bibliometrics.

We searched the Web of Science Core Collection database (WOSCC) for relevant literature published from 2011 to 2024. We used VOSviewer and Citespace to analyze countries, institutions, authors, keywords, highly cited references, and co-cited references.

3105 pieces of literatures were included in the research analysis, and PEOPLES R CHINA and the USA took the leading position in the number of papers published and had academic influence. The Chinese Academy of Sciences posted the most papers. The most prolific scholar was Abnous Khalil. The level of economic development is inversely proportional to the number of cases and deaths of colorectal cancer. Nanoparticles (NPs), the nanomedical drug delivery system (NDDS) is a hot topic in the field. Photodynamic therapy (PDT), immunogenic cell death (ICD), tumor microenvironment (TEM), folic acid, and pH are the cutting edge of the field.

This paper introduces the research hotspot, emphasis, and frontier of CRC and nanomedicine, and points out the direction for this field.

There is a great deal of research interest in the design of alternative metallodrugs to Pt(II)-derivatives for cancer treatment. The low solubility of such drugs in biological mediums leading to poor bioavailability is the major hurdle of several metal-based anticancer agents. These issues have recently been addressed by designing bio-active ligands based on metal-containing anticancer agents. Conjugating with bioactive ligands has significantly improved the bioavailability of the metallodrugs and their cancer cell targeting ability. One such naturally available bioactive ligand is curcumin. Until recently, several curcumin-based anticancer metallodrugs have been developed and successfully demonstrated for their anticancer studies. In this article, we aim to highlight, the synthesis, structure, and anticancer properties of various Zn(II)-curcumin-based coordination complexes. The effect of introducing different functional groups, targeting ligands, and photo-active ligands on the anticancer potential of such complexes has been mentioned in detail. The current status and future perspective on curcumin-based metallodrugs for cancer treatment have also been stated.

The goal of the research was to develop a hydrophobic octanoate salt of chitosan (CS-OA) and use the salt as a nanoparticle platform for the delivery of curcumin (CUR) into prostate cancer cells. The nanoprecipitation technique was used to prepare the nanoparticles, which were measured for particle size and encapsulation efficacy relative to CUR-CS nanoparticles. The cytotoxicity of CUR-OA-CS nanoparticles was evaluated in prostate cancerous cells (PC3 and DU145) in comparison with the corresponding blank nanoparticles and hydroalcoholic CUR solution. PXRD, SEM, and TEM were also used to examine the CUR-CS-OA nanoparticles. The average diameters of the CUR-CS-OA and CUR-CS nanoparticles were 268.90 ± 3.77 nm and 221.90 ± 2.79 nm, respectively, with encapsulation efficiencies of 61.37 ± 1.70% and 60.20 ± 3.17%. PXRD and SEM suggested CUR amorphization in the CS-OA nanoparticles. The void nanoparticles exhibited concentration-dependent antiproliferative action, which was attributed to the cellular uptake of CS. CUR loading into these nanoparticles increased their cytotoxicity even more. The potential of CS-OA nanoparticles as a special delivery system for additional cytotoxic drugs into different malignant cells can be further explored.

The application of multidisciplinary techniques in the management of endocrine-related cancers is crucial for harnessing the advantages of multiple disciplines and their coordinated efforts in eliminating tumors. Due to the malignant characteristics of cancer cells, they possess the capacity to develop resistance to traditional treatments such as chemotherapy and radiotherapy. Nevertheless, despite diligent endeavors to enhance the prediction of outcomes, the overall survival rate for individuals afflicted with endocrine-related malignancy remains quite miserable. Hence, it is imperative to investigate innovative therapy strategies. The latest advancements in therapeutic tactics have offered novel approaches for the therapy of various endocrine tumors. This paper examines the advancements in nano-drug delivery techniques and the utilization of nanomaterials for precise cancer cures through targeted therapy. This review provides a thorough analysis of the potential of combined drug delivery strategies in the treatment of thyroid cancer, adrenal gland tumors, and pancreatic cancer. The objective of this study is to gain a deeper understanding of current therapeutic approaches, stimulate the development of new drug DDS, and improve the effectiveness of treatment for patients with these diseases. The intracellular uptake of pharmaceuticals into cancer cells can be significantly improved through the implantation of synthetic or natural substances into nanoparticles, resulting in a substantial reduction in the development of endocrine malignancies.

Peroxynitrite (ONOO-) plays a crucial role in maintaining cellular redox homeostasis and regulating diffusive processes, cellular transport, and signal transduction. Extensive studies have revealed that increased ONOO- levels during tumor progression are associated with heightened levels of oxidative stress. However, current methods lack noninvasive visualization, immediate reporting, and highly sensitive fluorescence sensing. In light of this, we have designed a biomimetic fluorescent nanoplatform, named Z-C-T@CM, for peroxynitrite-responsive near-infrared fluorescent imaging guided cancer treatment. The nanoplatform comprises tetrakis(4-carboxyphenyl) porphyrin (TCPP) and curcumin (CCM) encapsulated within a zeolitic imidazolate framework-8 (ZIF-8), which is coated with a mouse breast cancer cell membrane for enhanced biocompatibility and targeting, while evading immune clearance. In vitro experimental results demonstrate that the as-prepared nanoplatform exhibits enhanced near-infrared fluorescence emission upon exposure to ONOO-, indicating a significant potential for noninvasive in vivo imaging of ONOO- during tumor progression. Additionally, Z-C-T@CM readily degrades in the tumor microenvironment, releasing TCPP and CCM, enabling a synergistic chemo-photodynamic therapy with near-infrared illumination. Further investigations indicate that Z-C-T@CM efficiently stimulates a tumor immune response and facilitates therapeutic efficiency. Collectively, this work introduces a novel noninvasive strategy for ONOO- detection, shedding new light on the integration of cancer diagnosis and efficient treatment.

Lymphoma, a malignancy of the lymphatic system, which is critical for maintaining the body's immune defenses, has become a focal point in recent research due to its intricate interplay with neutrophils-white blood cells essential for combating infections and inflammation. Unlike prior perceptions associating neutrophils only with tumor support, contemporary studies underscore their intricate and multifaceted involvement in the immune response to lymphoma. Recognizing the nuanced participation of neutrophils in lymphoma is crucial for developing innovative treatments to improve patient outcomes.

Targeted protein degradation (TPD) has emerged as a prominent and vital strategy for therapeutic intervention of cancers and other diseases. One such approach involves the exploration of proteolysis targeting chimeras (PROTACs) for the selective elimination of disease-causing proteins through the innate ubiquitin-proteasome pathway. Due to the unprecedented achievements of various PROTAC molecules in clinical trials, researchers have moved towards other physiological protein degradation approaches for the targeted degradation of abnormal proteins, including lysosome-targeting chimeras (LYTACs), autophagy-targeting chimeras (AUTACs), autophagosome-tethering compounds (ATTECs), molecular glue degraders, and other derivatives for their precise mode of action. Despite numerous advantages, these molecules face challenges in solubility, permeability, bioavailability, and potential off-target or on-target off-tissue effects. Thus, an urgent need arises to direct the action of these degrader molecules specifically against cancer cells, leaving the proteins of non-cancerous cells intact. Recent advancements in TPD have led to innovative delivery methods that ensure the degraders are delivered in a cell- or tissue-specific manner to achieve cell/tissue-selective degradation of target proteins. Such receptor-specific active delivery or nano-based passive delivery of the PROTACs could be achieved by conjugating them with targeting ligands (antibodies, aptamers, peptides, or small molecule ligands) or nano-based carriers. These techniques help to achieve precise delivery of PROTAC payloads to the target sites. Notably, the successful entry of a Degrader Antibody Conjugate (DAC), ORM-5029, into a phase 1 clinical trial underscores the therapeutic potential of these conjugates, including LYTAC-antibody conjugates (LACs) and aptamer-based targeted protein degraders. Further, using bispecific antibody-based degraders (AbTACs) and delivering the PROTAC pre-fused with E3 ligases provides a solution for cell type-specific protein degradation. Here, we highlighted the current advancements and challenges associated with developing new tumour-specific protein degrader approaches and summarized their potential as single agents or combination therapeutics for cancer.

The incidence of head and neck cancers, particularly those associated with Human Papillomavirus (HPV) infections, has been steadily increasing. Conventional therapies exhibit limitations and drawbacks, prompting the exploration of new strategies over the years, with nanomedicine approaches, especially liposomes gaining relevance. Additionally, the functionalization of liposomes with aptamers enables selective delivery to target cells. For instance, AT11 can serve as a targeting moiety for cancer cells due to its high affinity for nucleolin, a protein overexpressed on the cancer cell's surface. In this study, liposomes functionalized with AT11 are proposed as drug delivery systems for imiquimod (IQ), aiming to maximize its potential as an anticancer agent for HPV-related cancers. To this end, firstly liposomes were produced through the ethanol injection method, functionalized with AT11-TEG-Cholesteryl, and characterized using dynamic light scattering. The obtained liposomes presented suitable properties for cancer therapy (with sizes from 120 to 140 nm and low polydispersity PDI < 0.16) and were further evaluated in terms of potential anticancer effects. AT11 IQ-associated liposomes allowed a selective delivery of IQ towards a tongue cancer cell line (UPCI-SCC-154) relative to the non-malignant cell line (Het1A). Specifically, they induced a selective reduction of the cell viability (∼52 % versus ∼113 %; p < 0.0001), proliferation (∼68 % versus ∼102 %; p<0.0001) and increased cell death (∼7-fold increase; p < 0.0001)). Additionally, they decreased the migration (from ∼24 % to ∼8 %; p < 0.0001) and invasion (to 11 %; p = 0.0047) capacities of the cancer cells. In summary, the produced liposomes represent a promising approach to enhance the anticancer potential of IQ in head and neck cancer, particularly in tongue cancer.

PI3K-AKT-mTOR plays as important role in the growth, metabolism, proliferation, and migration of cancer cells, and in apoptosis, autophagy, inflammation, and angiogenesis in cancer. In this study, the aim was to comprehensively review the current research landscape regarding the PI3K-AKT-mTOR pathway in cancer, using bibliometrics to analyze research hotspots, and provide ideas for future research directions. Literature published on the topic between January 2006 and May 2023 was retrieved from the Web of Science core database, and key information and a visualization map were analyzed using CiteSpace and VOSviewer. A total of 5800 articles from 95 countries/regions were collected, including from China and the USA. The number of publications on the topic increased year on year. The major research institution was the University of Texas MD Anderson Cancer Center. Oncotarget and Clinical Cancer Research were the most prevalent journals in the field. Of 26,621 authors, R Kurzrock published the most articles, and J Engelman was cited most frequently. "A549 cell," "first line treatment," "first in human phase I," and "inhibitor" were the keywords of emerging research hotspots. Inhibitors of the PI3K-AKT-mTOR pathway and their use in clinical therapeutic strategies for cancer were the main topics in the field, and future research should also focus on PI3K-AKT-mTOR pathway inhibitors. This study is the first to comprehensively summarize trends and development s in research into the PI3K-AKT-mTOR pathway in cancer. The information that was obtained clarified recent research frontiers and directions, providing references for scholars of cancer management.

A monster called cancer is still one of the most challenging human problems and one of the leading causes of death in the world. Different types of treatment methods are used for cancer therapy; however, there are challenges such as high cost and harmful side effects in using these methods. Recent years have witnessed a surge in the development of therapeutic peptides for a wide range of diseases, notably cancer. Peptides are preferred over antibiotics, radiation therapy, and chemotherapy in the treatment of cancer due to a number of aspects, including flexibility, easy modification, low immunogenicity, and inexpensive cost of production. The use of therapeutic peptides in cancer treatment is a novel and intriguing strategy. These peptides provide excellent prospects for targeted drug delivery because of their high selectivity, specificity, small dimensions, good biocompatibility, and simplicity of modification. Target specificity and minimal toxicity are benefits of therapeutic peptides. Additionally, peptides can be used to design antigens or adjuvants for vaccine development. Here, types of therapeutic peptides for cancer therapy will be discussed, such as peptide-based cancer vaccines and tumor-targeting peptides (TTP) and cell-penetrating peptides (CPP).

Multiwalled carbon nanotubes (MWCNTs) are at the forefront of nanotechnology-based advancements in cancer therapy, particularly in the field of targeted drug delivery. The nanotubes are characterized by their concentric graphene layers, which give them outstanding structural strength. They can deliver substantial doses of therapeutic agents, potentially reducing treatment frequency and improving patient compliance. MWCNTs' diminutive size and modifiable surface enable them to have a high drug loading capacity and penetrate biological barriers. As a result of the extensive research on these nanomaterials, they have been studied extensively as synthetic and chemically functionalized molecules, which can be combined with various ligands (such as folic acid, antibodies, peptides, mannose, galactose, polymers) and linkers, and to deliver anticancer drugs, including but not limited to paclitaxel, docetaxel, cisplatin, doxorubicin, tamoxifen, methotrexate, quercetin and others, to cancer cells. This functionalization facilitates selective targeting of cancer cells, as these ligands bind to specific receptors overexpressed in tumor cells. By sparing non-cancerous cells and delivering the therapeutic payload precisely to cancer cells, this therapeutic payload delivery ability reduces chemotherapy systemic toxicity. There is great potential for MWCNTs to be used as targeted delivery systems for drugs. In this review, we discuss techniques for functionalizing and conjugating MWCNTs to drugs using natural and biomacromolecular linkers, which can bind to the cancer cells' receptors/biomolecules. Using MWCNTs to administer cancer drugs is a transformative approach to cancer treatment that combines nanotechnology and pharmacotherapy. It is an exciting and rich field of research to explore and optimize MWCNTs for drug delivery purposes, which could result in significant benefits for cancer patients.

Of the different modalities used to treat retinoblastoma, a chemothermotherapeutic regimen combining carboplatin and thermotherapy (also termed focal therapy), and the application of melphalan as a monotherapy, are particularly successful. Some studies indicate that melphalan shows potential when applied in combination with focal therapy, and yet is not applied in this combination. Here we describe a series of synthetically modified melphalan derivatives that display enhanced cytotoxicity relative to melphalan itself, with some displaying further enhancements in cytotoxicity when applied in combination with heat (used as a model for thermotherapy). The synthetic approach, which involves modifying melphalan with perfluorous chains of varying lengths via an ester linker, could lead to a more effective treatment option for retinoblastoma with reduced side-effects, which is a key limitation of melphalan.

Cellular senescence is an important risk factor in the development of hepatic steatosis. Senolytics present therapeutic effects on age-related hepatic steatosis without eliminating senescent hepatocytes directly. Therefore, it highlights the need to find senolytics' therapeutic targets. Dysfunction of adipose tissue underlies the critical pathogenesis of lipotoxicity in the liver. However, the correlation between adipose tissue and hepatic steatosis during aging and its underlying molecular mechanism remains poorly understood. We explored the correlation between white adipose tissue (WAT) and the liver during aging and evaluated the effect of lipolysis of aged WAT on hepatic steatosis and hepatocyte senescence. We screened out the ideal senolytics for WAT and developed a WAT-targeted delivery system for senotherapy. We assessed senescence and lipolysis of WAT and hepatic lipid accumulation after treatment. The results displayed that aging accelerated cellular senescence and facilitated lipolysis of WAT. Free fatty acids (FFAs) generated by WAT during aging enhanced hepatic steatosis and induced hepatocyte senescence. The combined usage of dasatinib and quercetin was screened out as the ideal senolytics to eliminate senescent cells in WAT. To minimize non-specific distribution and enhance the effectiveness of senolytics, liposomes decorated with WAT affinity peptide P3 were constructed for senotherapy in vivo. In vivo study, WAT-targeted treatment eliminated senescent cells in WAT and reduced lipolysis, resulting in the alleviation of hepatic lipid accumulation and hepatocyte senescence when compared to non-targeted treatment, providing a novel tissue-targeted, effective and safe senotherapy for age-related hepatic steatosis.

Cancer stands as a leading cause of global mortality, with chemotherapy being a pivotal treatment approach, either alone or in conjunction with other therapies. The primary goal of these therapies is to inhibit the growth of cancer cells specifically, while minimizing harm to healthy dividing cells. Conventional treatments, often causing patient discomfort due to side effects, have led researchers to explore innovative, targeted cancer cell therapies. Thus, biopolymer-based aerogels emerge as innovative platforms, showcasing unique properties that respond intelligently to diverse stimuli. This responsiveness enables precise control over the release of anticancer drugs, enhancing therapeutic outcomes. The significance of these aerogels lies in their ability to offer targeted drug delivery with increased efficacy, biocompatibility, and a high drug payload. In this comprehensive review, the author discuss the role of biopolymer-based aerogels as an emerging functionalized platforms in anticancer drug delivery. The review addresses the unique properties of biopolymer-based aerogels showing their smart behavior in responding to different stimuli including temperature, pH, magnetic and redox potential to control anticancer drug release. Finally, the review discusses the application of different biopolymer-based aerogel in delivering different anticancer drugs and also discusses the potential of these platforms in gene delivery applications.

A unitary model of drug release dynamics is proposed, assuming that the polymer-drug system can be assimilated into a multifractal mathematical object. Then, we made a description of drug release dynamics that implies, via Scale Relativity Theory, the functionality of continuous and undifferentiable curves (fractal or multifractal curves), possibly leading to holographic-like behaviors. At such a conjuncture, the Schrödinger and Madelung multifractal scenarios become compatible: in the Schrödinger multifractal scenario, various modes of drug release can be "mimicked" (via period doubling, damped oscillations, modulated and "chaotic" regimes), while the Madelung multifractal scenario involves multifractal diffusion laws (Fickian and non-Fickian diffusions). In conclusion, we propose a unitary model for describing release dynamics in polymer-drug systems. In the model proposed, the polymer-drug dynamics can be described by employing the Scale Relativity Theory in the monofractal case or also in the multifractal one.

Drugs that form self-assembled supramolecular structures to be most-active is a promising way of creating new highly specific and active pharmaceuticals. Controlling the activity of bioactive supramolecular structures such as drug-loaded micelles is possible by both core/shell and inter-assembly cross-linking. However, if the flexibility of the assembly is mandatory for the activity cross-linking is not feasible. Thus, such structures cannot be manipulated in their activity. The present study demonstrates a novel concept to control the activity of not drug-releasing, non-cross-linked bioactive superstructures. This is achieved by formation of nanostructured nanoparticles derived by non-covalent inter-assembly cross-linking of the superstructures. This is shown on the example of amphiphilic diblock-copolymers conjugated with the antibiotic ciprofloxacin (CIP). These polymer-antibiotic conjugates form worm micelles, which greatly activate the conjugated antibiotic without releasing it. Non-covalent inter-assembly cross-linking of these CIP-worm-micelles with amphiphilic triblock copolymers terminated with lipase-cleavable esters leads to nanostructured nanoparticles that resemble cross-linked worm micelles and show an up to 135-fold lower activity than the free worm micelles. The activity of the worm-micelles can be fully recovered by cleaving the end groups of the polymeric cross-linker with lipase.

Interest in multifunctional polymer nanoparticles for targeted delivery of anti-cancer drugs has grown significantly in recent years. In this study, tumor-targeting echogenic polymer micelles were prepared from poly(ethylene glycol) methyl ether-alkyl carbonate (mPEG-AC) derivatives, and their potential in cancer therapy was assessed. Various mPEG derivatives with carbonate linkages were synthesized via an alkyl halide reaction between mPEG and alkyl chloroformate. Micelle formation using polymer amphiphiles in aqueous media and the subsequent carbon dioxide (CO2) gas generation from the micelles was confirmed. Their ability to target neuroblastoma was substantially enhanced by incorporating the rabies virus glycoprotein (RVG) peptide. RVG-modified gas-generating micelles significantly inhibited tumor growth in a tumor-bearing mouse model owing to CO2 gas generation within tumor cells and resultant cytolytic effects, showing minimal side effects. The development of multifunctional polymer micelles may offer a promising therapeutic approach for various diseases, including cancer.

Studies of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in resectable non-small-cell lung cancer (NSCLC) have been conducted. The purpose of our study was to evaluate the benefits of osimertinib as neoadjuvant therapy for resectable EGFR-mutated NSCLC.

This retrospective study evaluated patients with EGFR mutations in exon 19 or 21 who received targeted therapy with osimertinib (80 mg per day) before surgery between January 2019 and October 2023 in Henan Cancer Hospital.

Twenty patients were evaluated, all of whom underwent surgery. The rate of R0 resection was 100% (20/20). The objective response rate was 80% (16/20), and the disease control rate was 95% (19/20). Postoperative pathological analysis showed a 25% (5/20) major pathological response rate and 15% (3/20) pathological complete response rate. In total, 25% (5/20) developed adverse events (AEs), and the rate of grades 3-4 AEs was 10% (2/20). One patient experienced a grade 3 skin rash, and 1 patient experienced grade 3 diarrhea.

Osimertinib as neoadjuvant therapy for resectable EGFR-mutated NSCLC is safe and well tolerated. Osimertinib has the potential to improve the radical resection rate and prognosis.

Colorectal cancer (CRC) is a widespread cancer that starts in the digestive tract. It is the third most common cause of cancer deaths around the world. The World Health Organization (WHO) estimates an expected death toll of over 1 million cases annually. The limited therapeutic options as well as the drawbacks of the existing therapies necessitate the development of non-classic treatment approaches. Nanotechnology has led the evolution of valuable drug delivery systems thanks to their ability to control drug release and precisely target a wide variety of cancers. This has also been extended to the treatment of CRC. Herein, we shed light on the pertinent research that has been performed on the potential applications of nanoparticles in the treatment of CRC. The various types of nanoparticles in addition to their properties, applications, targeting approaches, merits, and demerits are discussed. Furthermore, innovative therapies for CRC, including gene therapies and immunotherapies, are also highlighted. Eventually, the research gaps, the clinical potential of such delivery systems, and a future outlook on their development are inspired.

Phototherapy, such as photothermal therapy (PTT) and photodynamic therapy (PDT), has been considered an elegant solution to eradicate tumors due to its minimal invasiveness and low systemic toxicity. Nevertheless, it is still challenging for phototherapy to achieve ideal outcomes and clinical translation due to its inherent drawbacks. Owing to the unique biological functions, diverse gases have attracted growing attention in combining with phototherapy to achieve super-additive therapeutic effects. Specifically, gases such as nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S) have been proven to kill tumor cells by inducing mitochondrial damage in synergy with phototherapy. Additionally, several gases not only enhance the thermal damage in PTT and the reactive oxygen species (ROS) production in PDT but also improve the tumor accumulation of photoactive agents. The inflammatory responses triggered by hyperthermia in PTT are also suppressed by the combination of gases. Herein, we comprehensively review the latest studies on gas-synergized phototherapy for cancer therapy, including (1) synergistic mechanisms of combining gases with phototherapy; (2) design of nanoplatforms for gas-synergized phototherapy; (3) multimodal therapy based on gas-synergized phototherapy; (4) imaging-guided gas-synergized phototherapy. Finally, the current challenges and future opportunities of gas-synergized phototherapy for tumor treatment are discussed. STATEMENT OF SIGNIFICANCE: 1. The novelty and significance of the work with respect to the existing literature. (1) Strategies to design nanoplatforms for gas-synergized anti-tumor phototherapy have been summarized for the first time. Meanwhile, the integration of various imaging technologies and therapy modalities which endow these nanoplatforms with advanced theranostic capabilities has been summarized. (2) The mechanisms by which gases synergize with phototherapy to eradicate tumors are innovatively and comprehensively summarized. 2. The scientific impact and interest. This review elaborates current trends in gas-synergized anti-tumor phototherapy, with special emphases on synergistic anti-tumor mechanisms and rational design of therapeutic nanoplatforms to achieve this synergistic therapy. It aims to provide valuable guidance for researchers in this field.

Docetaxel (DOC) is commonly used in cancer treatment, especially for breast cancer. However, there are severe side effects in clinical application. In order to deliver docetaxel more effectively, a novel, active targeting acid-responsive polymer called cRGD-PAE-PEG-DSPE was developed. The polymer structure incorporated poly(ethylene glycol) (PEG) as the hydrophilic segment, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) as the hydrophobic segment, and poly(β-amino ester) (PAE) as the acid-responsive group, which was grafted onto the PEG. Furthermore, c(RGDyC) was grafted onto PAE to confer active targeting capability. Through self-assembly, docetaxel was encapsulated in RAED@DOC. Through in vitro experiments, it was confirmed that RAED@DOC had good serum stability and acid responsiveness, as well as enhanced uptake by MDA-MB-231 cells. Additionally, the antitumor efficiency in vivo and histopathological analysis showed that RAED@DOC exhibited higher antitumor activity and lower systemic toxicity in comparison to free docetaxel. These results suggested that RAED@DOC had considerable potential clinical use.

Clinically, the immune checkpoint inhibitor anti-PD-1 antibody has shown a certain effect in the treatment of hepatocellular carcinoma (HCC), which is limited to a small number of patients with HCC. This study aims to reveal whether carnosic acid nanocluster-based framework (CA-NBF) has a sensitization effect on anti-PD-1 antibody in the treatment of HCC at the cellular and animal levels. MHCC97H cells were treated with CA-NBF, anti-PD-1 and their combination. The effects of CA-NBF and anti-PD-1 on cell proliferation, cell cycle, apoptosis, invasion, and migration were evaluated by MTT assay, flow cytometry, and scratch test. The effects of CA-NBF and anti-PD-1 on Wnt/β-catenin signaling pathway in MHCC97H cells were detected. A BALB/C nude mouse model of hepatocellular carcinoma was established, and the tumor growth was observed at different time points. The expression of cytotoxic T lymphocyte and helper T lymphocyte markers CD8 and CD4 in tumor tissues was detected by immunohistochemistry. Western blotting was used to detect the Wnt/β-catenin signaling pathway proteins (Wnt-3a, β-catenin, and GSK-3β) level in tumor tissues after CA-NBF and anti-PD-1 treatment. CA-NBF activity was significantly higher than CA, which could prominently reduce the proliferation, migration and invasion of MHCC97H cells and enhance apoptosis by inactivating Wnt/β-catenin signaling pathway. CA-NBF combined with anti-PD-1 antibody further enhanced cell proliferation, migration, invasion and pro-apoptosis but had no significant effect on Wnt/β-catenin signaling pathway. CA-NBF in vivo improved the tumor response to PD1 immune checkpoint blockade in HCC, manifested by reducing tumor size and weight, promoting CD4 and CD8 expression. CA-NBF combined with anti-PD-1 have stronger immunomodulatory and anticancer effects without increasing biological toxicity.

Chemotherapy is the mainstay of cancer treatment, bringing patients optimism about recurrence and survival. However, the clinical effectiveness of chemotherapeutic drugs is frequently jeopardized by their intrinsic toxicity, resulting in side effects affecting the quality of life of cancer patients. This analysis explores the ethnopharmacological impact of phytopharmaceuticals, highlighting their traditional use in many cultures. The present study, which takes its cues from indigenous knowledge, aims to close the knowledge gap between traditional medicine and modern medicine in reducing the toxicities of chemotherapy treatments.

The present in-depth study aims to highlight the current research and upcoming developments in phytopharmaceuticals for reducing the toxicity of chemotherapeutic drugs. Further, we address the mechanisms through which phytopharmaceuticals may reduce chemotherapy-induced side effects that include nausea, vomiting, myelosuppression, nephropathy, neuropathy, and cardiotoxicity using data from a variety of preclinical and clinical investigations.

The literature search was carried out by employing search engines such as PubMed and Google Scholar with keywords such as cancer, chemotherapy, CNS toxicity, hematopoietic toxicity, renal toxicity, GI toxicity, CNS toxicity, and phytopharmaceuticals.

Bioactive chemicals found in plants, such as fruits, vegetables, herbs, and spices, are being studied for their capacity to improve the safety and acceptability of chemotherapy regimens. The current review also dives into the investigation of phytopharmaceuticals as adjuvant medicines in cancer treatment, which is a viable path for addressing the pressing need to lessen chemotherapy-induced toxicities.

The present review revealed that the potential of phytopharmaceuticals in alleviating chemotherapeutic drug toxicities would pave the way for better cancer treatment and patient outcomes, harmonizing with the larger trend towards personalized and holistic approaches to chemotherapy.

A significant fraction of non-small cell lung cancer (NSCLC) cases are due to oncogenic mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR). Anti-EGFR antibodies have shown limited clinical benefit for NSCLC, whereas tyrosine kinase inhibitors (TKIs) are effective, but resistance ultimately occurs. The current landscape suggests that alternative ligands that target wild-type and mutant EGFRs are desirable for targeted therapy or drug delivery development. Here we evaluate NSCLC targeting using an anti-EGFR aptamer (MinE07). We demonstrate that interaction sites of MinE07 overlap with clinically relevant antibodies targeting extracellular domain III and that MinE07 retains binding to EGFR harboring the most common oncogenic and resistance mutations. When MinE07 was linked to an anti-c-Met aptamer, the EGFR/c-Met bispecific aptamer (bsApt) showed superior labeling of NSCLC cells in vitro relative to monospecific aptamers. However, dual targeting in vivo did not improve the recognition of NSCLC xenografts compared to MinE07. Interestingly, biodistribution of Cy7-labeled bsApt differed significantly from Alexa Fluor 750-labeled bsApt. Overall, our findings demonstrate that aptamer formulations containing MinE07 can target ectopic lung cancer without additional stabilization or PEGylation and highlights the potential of MinE07 as a targeting reagent for the recognition of NSCLC harboring clinically relevant EGFRs.

The rapid development of nanomedicines is revolutionizing the landscape of cancer treatment, while effectively delivering them into solid tumors remains a formidable challenge. Currently, there is a huge disconnect on therapeutic response between regulatory approved nanomedicines and laboratory reported nanoparticles. The discrepancy is mainly resulted from the failure of using the classic overall pharmacokinetics behaviors of nanomedicines in tumors to predict the antitumor efficacy. Increasing evidence has revealed that the therapeutic efficacy predominantly relies on the intratumoral spatiotemporal distribution of nanomedicines. This review focuses on the spatiotemporal distribution of systemically administered chemotherapeutic nanomedicines in solid tumor. Firstly, the intratumoral biological barriers that regulate the spatiotemporal distribution of nanomedicines are described in detail. Next, the influences on antitumor efficacy caused by the spatial distribution and temporal drug release of nanomedicines are emphatically analyzed. Then, current methodologies for evaluating the spatiotemporal distribution of nanomedicines are summarized. Finally, the advanced strategies to positively modulate the spatiotemporal distribution of nanomedicines for an optimal tumor therapy are comprehensively reviewed.

Upon entering the biological milieu, nanomedicines swiftly interact with the surrounding tissue fluid, subsequently being enveloped by a dynamic interplay of biomacromolecules, such as carbohydrates, nucleic acids, and cellular metabolites, but with predominant serum proteins within the biological corona. A notable consequence of the protein corona phenomenon is the unintentional loss of targeting ligands initially designed to direct nanomedicines toward particular cells or organs within the in vivo environment. mRNA nanomedicine displays high demand for specific cell and tissue-targeted delivery to effectively transport mRNA molecules into target cells, where they can exert their therapeutic effects with utmost efficacy. In this review, focusing on the delivery systems and tissue-specific applications, we aim to update the nanomedicine population with the prevailing and still enigmatic paradigm of nano-bio interactions, a formidable hurdle in the pursuit of targeted mRNA delivery. We also elucidate the current impediments faced in mRNA therapeutics and, by contemplating prospective avenues-either to modulate the corona or to adopt an 'ally from adversary' approach-aim to chart a course for advancing mRNA nanomedicine.

Polymeric drug delivery technology, which allows for medicinal ingredients to enter a cell more easily, has advanced considerably in recent decades. Innovative medication delivery strategies use biodegradable and bio-reducible polymers, and progress in the field has been accelerated by future possible research applications. Natural polymers utilized in polymeric drug delivery systems include arginine, chitosan, dextrin, polysaccharides, poly(glycolic acid), poly(lactic acid), and hyaluronic acid. Additionally, poly(2-hydroxyethyl methacrylate), poly(N-isopropyl acrylamide), poly(ethylenimine), dendritic polymers, biodegradable polymers, and bioabsorbable polymers as well as biomimetic and bio-related polymeric systems and drug-free macromolecular therapies have been employed in polymeric drug delivery. Different synthetic and natural biomaterials are in the clinical phase to mitigate different diseases. Drug delivery methods using natural and synthetic polymers are becoming increasingly common in the pharmaceutical industry, with biocompatible and bio-related copolymers and dendrimers having helped cure cancer as drug delivery systems. This review discusses all the above components and how, by combining synthetic and biological approaches, micro- and nano-drug delivery systems can result in revolutionary polymeric drug and gene delivery devices.

We report a fluorescent dye TM by incorporating the tetraphenylethylene (TPE) and cholesterol components into perylene bisimides (PBI) derivative. Fluorescence emission spectrum shows that the dye has stable red emission and aggregation-induced emission (AIE) characteristics. The incorporation of cholesterol components triggers TM to show induced chirality through supramolecular self-assembly. The cRGD-functionalized nanoparticles were prepared by encapsulating fluorescent dyes with amphiphilic polymer matrix. The functionalized fluorescent organic nanoparticles exhibit excellent biocompatibility, large Stokes' shift and good photostability, which make them effective fluorescent probes for targeting cancer cells with high fluorescence contrast.

Two BODIPY-biotin conjugates KDP1 and KDP2 are designed and synthesized for targeted PDT applications. Both have good absorption with a high molar absorption coefficient and decent singlet oxygen generation quantum yields. The photosensitizers KDP1 and KDP2 were found to be localized in the mitochondria with excellent photocytotoxicity of up to 18.7 nM in MDA-MB-231 breast cancer cells. The cell death predominantly proceeded through the apoptosis pathway via ROS production.

Messenger RNA (mRNA)-based therapy has emerged as a powerful, safe, and rapidly scalable therapeutic approach that involves technologies for both mRNA itself and the delivery vehicle. Although there are some unique challenges for different applications of mRNA therapy, a common challenge for all mRNA therapeutics is the transport of mRNA into the target cell cytoplasm for sufficient protein expression. This review is focused on the behaviors at the cellular level of nanotechnology-mediated mRNA delivery systems, which have not been comprehensively reviewed yet. First, the four main therapeutic applications of mRNA are introduced, including immunotherapy, protein replacement therapy, genome editing, and cellular reprogramming. Second, common types of mRNA cargos and mRNA delivery systems are summarized. Third, strategies to enhance mRNA delivery efficiency during the cellular trafficking process are highlighted, including accumulation to the cell, internalization into the cell, endosomal escape, release of mRNA from the nanocarrier, and translation of mRNA into protein. Finally, the challenges and opportunities for the development of nanotechnology-mediated mRNA delivery systems are presented. This review can provide new insights into the future fabrication of mRNA nanocarriers with desirable cellular trafficking performance.

Radiosurgery has been recognized as a reasonable treatment for metastatic brain tumors. Increasing the radiosensitivity and synergistic effects are possible ways to improve the therapeutic efficacy of specific regions of tumors. c-Jun-N-terminal kinase (JNK) signaling regulates H2AX phosphorylation to repair radiation-induced DNA breakage. We previously showed that blocking JNK signaling influenced radiosensitivity in vitro and in an in vivo mouse tumor model. Drugs can be incorporated into nanoparticles to produce a slow-release effect. This study assessed JNK radiosensitivity following the slow release of the JNK inhibitor SP600125 from a poly (DL-lactide-co-glycolide) (LGEsese) block copolymer in a brain tumor model.

A LGEsese block copolymer was synthesized to fabricate SP600125-incorporated nanoparticles by nanoprecipitation and dialysis methods. The chemical structure of the LGEsese block copolymer was confirmed by 1H nuclear magnetic resonance (NMR) spectroscopy. The physicochemical and morphological properties were observed by transmission electron microscopy (TEM) imaging and measured with particle size analyzer. The blood-brain barrier (BBB) permeability to the JNK inhibitor was estimated by BBBflammaTM 440-dye-labeled SP600125. The effects of the JNK inhibitor were investigated using SP600125-incorporated nanoparticles and by optical bioluminescence, magnetic resonance imaging (MRI), and a survival assay in a mouse brain tumor model for Lewis lung cancer (LLC)-Fluc cells. DNA damage was estimated by histone γ H2AX expression and apoptosis was assessed by the immunohistochemical examination of cleaved caspase 3.

The SP600125-incorporated nanoparticles of the LGEsese block copolymer were spherical and released SP600125 continuously for 24h. The use of BBBflammaTM 440-dye-labeled SP600125 demonstrated the ability of SP600125 to cross the BBB. The blockade of JNK signaling with SP600125-incorporated nanoparticles significantly delayed mouse brain tumor growth and prolonged mouse survival after radiotherapy. γ H2AX, which mediates DNA repair protein, was reduced and the apoptotic protein cleaved-caspase 3 was increased by the combination of radiation and SP600125-incorporated nanoparticles.

Pancreatic cancer represents one of the most lethal cancer types worldwide, with a 5-year survival rate of less than 5%. Due to the inability to diagnose it promptly and the lack of efficacy of existing treatments, research and development of innovative therapies and new diagnostics are crucial to increase the survival rate and decrease mortality. Nanomedicine has been gaining importance as an innovative approach for drug delivery and diagnosis, opening new horizons through the implementation of smart nanocarrier systems, which can deliver drugs to the specific tissue or organ at an optimal concentration, enhancing treatment efficacy and reducing systemic toxicity. Varied materials such as lipids, polymers, and inorganic materials have been used to obtain nanoparticles and develop innovative drug delivery systems for pancreatic cancer treatment. In this review, it is discussed the main scientific advances in pancreatic cancer treatment by nano-based drug delivery systems. The advantages and disadvantages of such delivery systems in pancreatic cancer treatment are also addressed. More importantly, the different types of nanocarriers and therapeutic strategies developed so far are scrutinized.

Nanoparticles (NPs) are used to encapsulate therapeutic cargos and deliver them specifically to the target site. The intracellular trafficking of NPs dictates the NP-cargo distribution within different cellular compartments, and thus governs their efficacy and safety. Knowledge in this field is crucial to understand their biological fate and improve their rational design. However, there is a lack of methods that allow precise localization and quantification of individual NPs within distinct cellular compartments simultaneously. Here, we address this issue by proposing a correlative light and electron microscopy (CLEM) method combining direct stochastic optical reconstruction microscopy (dSTORM) and transmission electron microscopy (TEM). We aim at combining the advantages of both techniques to precisely address NP localization in the context of the cell ultrastructure. Individual fluorescently-labelled poly(lactide-co-glycolide)-poly(ethylene glycol) (PLGA-PEG) NPs were directly visualized by dSTORM and assigned to cellular compartments by TEM. We first tracked NPs along the endo-lysosomal pathway at different time points, then demonstrated the effect of chloroquine on their intracellular distribution (i.e. endosomal escape). The proposed protocol can be applied to fluorescently labelled NPs and/or cargo, including those not detectable by TEM alone. Our studies are of great relevance to obtain important information on NP trafficking, and crucial for the design of more complex nanomaterials aimed at cytoplasmic/nucleic drug delivery.

Prostate cancer (PCa) is one of the most prevalent cancer diagnoses among men in the United States and in several other developed countries. The prostate specific membrane antigen (PSMA) has been recognized as a promising molecular target in PCa, which has led to the development of specific radionuclide-based tracers for imaging and radiopharmaceuticals for PSMA targeted therapy. These compounds range from small molecule ligands to monoclonal antibodies (mAbs). Monoclonal antibodies play a crucial role in targeting cancer cell-specific antigens with a high degree of specificity while minimizing side effects to normal cells. The same mAb can often be labeled in different ways, such as with radionuclides suitable for imaging with Positron Emission Tomography (β+ positrons), Gamma Camera Scintigraphy (γ photons), or radiotherapy (β- electrons, α-emitters, or Auger electrons). Accordingly, the use of radionuclide-based PSMA-targeting compounds in molecular imaging and therapeutic applications has significantly grown in recent years. In this article, we will highlight the latest developments and prospects of radiolabeled mAbs that target PSMA for the detection and treatment of prostate cancer.