|
1
|
Tong Y, Gao M, Luo Y. Mesenchymal Stem Cell Membrane-Derived Composite System for Enhancing the Tumor Treatment Efficacy of Metal-Organic Framework Nanoparticles. IET Nanobiotechnol 2024; 2024:1069307. [PMID: 39669228 PMCID: PMC11637620 DOI: 10.1049/nbt2/1069307] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2024] [Accepted: 11/21/2024] [Indexed: 12/14/2024] Open
Abstract
Mesenchymal stem cell (MSC) membrane-coated metal-organic frameworks (MOFs) represent an innovative approach to enhance the uptake and therapeutic efficacy of copper-based MOFs (Cu-MOFs) in tumor cells. By leveraging the natural homing abilities and biocompatibility of MSC membranes, Cu-MOFs can be effectively targeted to tumor sites, promoting increased cellular uptake. This coating not only facilitates superior internalization by cancer cells but also augments the therapeutic outcomes due to the enhanced delivery of copper ions. In vitro studies demonstrate that MSC membrane-coated Cu-MOFs (MSC-Cu-MOFs) significantly improve the cytotoxic effects on tumor cells compared to uncoated Cu-MOFs. This novel strategy presents a promising avenue for advancing the precision and effectiveness of cancer treatment modalities, showcasing potential for clinical applications in oncology.
Collapse
Affiliation(s)
- Ying Tong
- Wuxi School of Medicine, Jiangnan University, Wuxi 214122, Jiangsu, China
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China
| | - Meng Gao
- Department of Gastroenterology, The Second People's Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University, Hefei 230011, Anhui, China
| | - Yingli Luo
- Wuxi School of Medicine, Jiangnan University, Wuxi 214122, Jiangsu, China
| |
Collapse
|
|
2
|
Tang J, Chen Y, Wang C, Xia Y, Yu T, Tang M, Meng K, Yin L, Yang Y, Shen L, Xing H, Mao X. The role of mesenchymal stem cells in cancer and prospects for their use in cancer therapeutics. MedComm (Beijing) 2024; 5:e663. [PMID: 39070181 PMCID: PMC11283587 DOI: 10.1002/mco2.663] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2024] [Revised: 06/26/2024] [Accepted: 07/01/2024] [Indexed: 07/30/2024] Open
Abstract
Mesenchymal stem cells (MSCs) are recruited by malignant tumor cells to the tumor microenvironment (TME) and play a crucial role in the initiation and progression of malignant tumors. This role encompasses immune evasion, promotion of angiogenesis, stimulation of cancer cell proliferation, correlation with cancer stem cells, multilineage differentiation within the TME, and development of treatment resistance. Simultaneously, extensive research is exploring the homing effect of MSCs and MSC-derived extracellular vesicles (MSCs-EVs) in tumors, aiming to design them as carriers for antitumor substances. These substances are targeted to deliver antitumor drugs to enhance drug efficacy while reducing drug toxicity. This paper provides a review of the supportive role of MSCs in tumor progression and the associated molecular mechanisms. Additionally, we summarize the latest therapeutic strategies involving engineered MSCs and MSCs-EVs in cancer treatment, including their utilization as carriers for gene therapeutic agents, chemotherapeutics, and oncolytic viruses. We also discuss the distribution and clearance of MSCs and MSCs-EVs upon entry into the body to elucidate the potential of targeted therapies based on MSCs and MSCs-EVs in cancer treatment, along with the challenges they face.
Collapse
Affiliation(s)
- Jian Tang
- Central LaboratoryXiangyang Central HospitalAffiliated Hospital of Hubei University of Arts and ScienceXiangyangChina
| | - Yu Chen
- Central LaboratoryXiangyang Central HospitalAffiliated Hospital of Hubei University of Arts and ScienceXiangyangChina
- Medical Affairs, Xiangyang Central HospitalAffiliated Hospital of Hubei University of Arts and ScienceXiangyangChina
| | - Chunhua Wang
- Department of Clinical LaboratoryXiangyang No. 1 People's HospitalHubei University of MedicineXiangyangHubei ProvinceChina
| | - Ying Xia
- Central LaboratoryXiangyang Central HospitalAffiliated Hospital of Hubei University of Arts and ScienceXiangyangChina
| | - Tingyu Yu
- Central LaboratoryXiangyang Central HospitalAffiliated Hospital of Hubei University of Arts and ScienceXiangyangChina
| | - Mengjun Tang
- Central LaboratoryXiangyang Central HospitalAffiliated Hospital of Hubei University of Arts and ScienceXiangyangChina
| | - Kun Meng
- Central LaboratoryXiangyang Central HospitalAffiliated Hospital of Hubei University of Arts and ScienceXiangyangChina
| | - Lijuan Yin
- State Key Laboratory of Food Nutrition and SafetyKey Laboratory of Industrial MicrobiologyMinistry of EducationTianjin Key Laboratory of Industry MicrobiologyNational and Local United Engineering Lab of Metabolic Control Fermentation TechnologyChina International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal ChemistryCollege of BiotechnologyTianjin University of Science & TechnologyTianjinChina
| | - Yang Yang
- Shenzhen Key Laboratory of Pathogen and ImmunityNational Clinical Research Center for Infectious DiseaseState Key Discipline of Infectious DiseaseShenzhen Third People's HospitalSecond Hospital Affiliated to Southern University of Science and TechnologyShenzhenChina
| | - Liang Shen
- Central LaboratoryXiangyang Central HospitalAffiliated Hospital of Hubei University of Arts and ScienceXiangyangChina
| | - Hui Xing
- Central LaboratoryXiangyang Central HospitalAffiliated Hospital of Hubei University of Arts and ScienceXiangyangChina
- Department of Obstetrics and GynecologyXiangyang Central HospitalAffiliated Hospital of Hubei University of Arts and SciencesXiangyangChina
| | - Xiaogang Mao
- Central LaboratoryXiangyang Central HospitalAffiliated Hospital of Hubei University of Arts and ScienceXiangyangChina
- Department of Obstetrics and GynecologyXiangyang Central HospitalAffiliated Hospital of Hubei University of Arts and SciencesXiangyangChina
| |
Collapse
|
|
3
|
Li Q, Geng T, Li H, Zheng S, Svedlund S, Gan L, Egnell AC, Gao S, Chen R, Hu P. Analysis of the pharmacokinetics and efficacy of RBD1016 - A GalNAc-siRNA targeting Hepatitis B Virus X gene using semi-mechanistic PK/PD model. Heliyon 2024; 10:e31924. [PMID: 38841435 PMCID: PMC11152740 DOI: 10.1016/j.heliyon.2024.e31924] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2023] [Revised: 05/23/2024] [Accepted: 05/23/2024] [Indexed: 06/07/2024] Open
Abstract
Small interference RNA (siRNA) is a class of short double-stranded RNA molecules that cause mRNA degradation through an RNA interference mechanism and is a promising therapeutic modality. RBD1016 is a siRNA drug in clinical development for the treatment of chronic Hepatitis B Virus (HBV) infection, which contains a conjugated with N-acetylglucosamine moiety that can facilitate its hepatic delivery. We aimed to construct a semi-mechanistic model of RBD1016 in pre-clinical animals, to elucidate the pharmacokinetic/pharmacodynamic (PK/PD) profiles in mice and PK profiles in monkeys, which can lay the foundation for potential future translation of RBD1016 PK and PD from the pre-clinical stage to the clinic stage. The proposed semi-mechanistic PK/PD model fitted PK and PD data in HBV transgenic mice well and described plasma and liver concentrations in the monkeys well. The simulation results showed that our model has a reasonable predictive ability for Hepatitis B surface antigen (HBsAg) levels after multiple dosing in mice. Further PK and PD data for RBD1016, including clinical data, will assist in refining the model presented here. Our current effort focused on model building for RBD1016, we anticipate that the model could apply to other GalNAc-siRNA drugs.
Collapse
Affiliation(s)
- Qian Li
- Clinical Pharmacology Research Center, Peking Union Medical College Hospital, State Key Laboratory of Complex Severe and Rare Diseases, NMPA Key Laboratory for Clinical Research and Evaluation of Drug, Beijing Key Laboratory of Clinical PK & PD Investigation for Innovative Drugs, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Taohua Geng
- Suzhou Ribo Life Science Co. Ltd., Jiangsu, 215300, China
| | - Haiyan Li
- Suzhou Ribo Life Science Co. Ltd., Jiangsu, 215300, China
| | - Shuquan Zheng
- Suzhou Ribo Life Science Co. Ltd., Jiangsu, 215300, China
| | - Sara Svedlund
- Ribocure Pharmaceuticals AB, Medicinaregatan 8A, Gothenburg, Sweden
| | - Liming Gan
- Suzhou Ribo Life Science Co. Ltd., Jiangsu, 215300, China
- Ribocure Pharmaceuticals AB, Medicinaregatan 8A, Gothenburg, Sweden
| | - Ann-Charlotte Egnell
- Suzhou Ribo Life Science Co. Ltd., Jiangsu, 215300, China
- Ribocure Pharmaceuticals AB, Medicinaregatan 8A, Gothenburg, Sweden
| | - Shan Gao
- Suzhou Ribo Life Science Co. Ltd., Jiangsu, 215300, China
| | - Rui Chen
- Clinical Pharmacology Research Center, Peking Union Medical College Hospital, State Key Laboratory of Complex Severe and Rare Diseases, NMPA Key Laboratory for Clinical Research and Evaluation of Drug, Beijing Key Laboratory of Clinical PK & PD Investigation for Innovative Drugs, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Pei Hu
- Clinical Pharmacology Research Center, Peking Union Medical College Hospital, State Key Laboratory of Complex Severe and Rare Diseases, NMPA Key Laboratory for Clinical Research and Evaluation of Drug, Beijing Key Laboratory of Clinical PK & PD Investigation for Innovative Drugs, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| |
Collapse
|
|
4
|
Nethi SK, Li X, Bhatnagar S, Prabha S. Enhancing Anticancer Efficacy of Chemotherapeutics Using Targeting Ligand-Functionalized Synthetic Antigen Receptor-Mesenchymal Stem Cells. Pharmaceutics 2023; 15:1742. [PMID: 37376189 DOI: 10.3390/pharmaceutics15061742] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2023] [Revised: 06/08/2023] [Accepted: 06/12/2023] [Indexed: 06/29/2023] Open
Abstract
Mesenchymal stem cells (MSCs) have been studied for their potential in facilitating tumor-targeted delivery of chemotherapeutics due to their tumor-homing characteristics. We hypothesized that targeting effectiveness of MSCs can be further enhanced by incorporating tumor-targeting ligands on MSC surfaces that will allow for enhanced arrest and binding within the tumor tissue. We utilized a unique strategy of modifying MSCs with synthetic antigen receptors (SARs), targeting specific antigens overexpressed on cancer cells. MSCs were surface-functionalized by first incorporating recombinant protein G (PG) on the surface, followed by binding of the targeting antibody to the PG handle. We functionalized MSCs with antibodies targeting a tyrosine kinase transmembrane receptor protein, epidermal growth factor receptor (EGFR), overexpressed in non-small-cell lung cancer (NSCLC). The efficacy of MSCs functionalized with anti-EGFR antibodies (cetuximab and D8) was determined in murine models of NSCLC. Cetuximab-functionalized MSCs demonstrated improved binding to EGFR protein and to EGFR overexpressing A549 lung adenocarcinoma cells. Further, cetuximab-functionalized MSCs loaded with paclitaxel nanoparticles were efficient in slowing orthotopic A549 tumor growth and improving the overall survival relative to that of other controls. Biodistribution studies revealed a six-fold higher retention of EGFR-targeted MSCs than non-targeted MSCs. Based on these results, we conclude that targeting ligand functionalization could be used to enhance the concentration of therapeutic MSC constructs at the tumor tissue and to achieve improved antitumor response.
Collapse
Affiliation(s)
- Susheel Kumar Nethi
- Fels Cancer Institute for Personalized Medicine, Lewis-Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA
| | - Xiaolei Li
- Fels Cancer Institute for Personalized Medicine, Lewis-Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA
| | | | - Swayam Prabha
- Fels Cancer Institute for Personalized Medicine, Lewis-Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA
- Department of Cancer and Cellular Biology, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA
- Molecular Therapeutics Program, Fox Chase Cancer Center, Temple University, Philadelphia, PA 19111, USA
| |
Collapse
|
|
5
|
Fan L, Wei A, Gao Z, Mu X. Current progress of mesenchymal stem cell membrane-camouflaged nanoparticles for targeted therapy. Biomed Pharmacother 2023; 161:114451. [PMID: 36870279 DOI: 10.1016/j.biopha.2023.114451] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Revised: 02/17/2023] [Accepted: 02/26/2023] [Indexed: 03/06/2023] Open
Abstract
Nanodrug delivery systems have been widely used in disease treatment. However, weak drug targeting, easy to be cleared by the immune system, and low biocompatibility are great obstacles for drug delivery. As an important part of cell information transmission and behavior regulation, cell membrane can be used as drug coating material which represents a promising strategy and can overcome these limitations. Mesenchymal stem cell (MSC) membrane, as a new carrier, has the characteristics of active targeting and immune escape of MSC, and has broad application potential in tumor treatment, inflammatory disease, tissue regeneration and other fields. Here, we review recent progress on the use of MSC membrane-coated nanoparticles for therapy and drug delivery, aiming to provide guidance for the design and clinical application of membrane carrier in the future.
Collapse
Affiliation(s)
- Lianlian Fan
- Department of Pharmacy, China-Japan Union Hospital, Jilin University, Changchun130033, China
| | - Anhui Wei
- Department of Regenerative Medicine, College of Pharmacy, Jilin University, Changchun130021, China
| | - Zihui Gao
- Changchun City Experimental High School, Changchun130117, China
| | - Xupeng Mu
- Scientific Research Center, China-Japan Union Hospital, Jilin University, Changchun130033, China.
| |
Collapse
|
|
6
|
Isaković J, Šerer K, Barišić B, Mitrečić D. Mesenchymal stem cell therapy for neurological disorders: The light or the dark side of the force? Front Bioeng Biotechnol 2023; 11:1139359. [PMID: 36926687 PMCID: PMC10011535 DOI: 10.3389/fbioe.2023.1139359] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2023] [Accepted: 02/13/2023] [Indexed: 03/08/2023] Open
Abstract
Neurological disorders are recognized as major causes of death and disability worldwide. Because of this, they represent one of the largest public health challenges. With awareness of the massive burden associated with these disorders, came the recognition that treatment options were disproportionately scarce and, oftentimes, ineffective. To address these problems, modern research is increasingly looking into novel, more effective methods to treat neurological patients; one of which is cell-based therapies. In this review, we present a critical analysis of the features, challenges, and prospects of one of the stem cell types that can be employed to treat numerous neurological disorders-mesenchymal stem cells (MSCs). Despite the fact that several studies have already established the safety of MSC-based treatment approaches, there are still some reservations within the field regarding their immunocompatibility, heterogeneity, stemness stability, and a range of adverse effects-one of which is their tumor-promoting ability. We additionally examine MSCs' mechanisms of action with respect to in vitro and in vivo research as well as detail the findings of past and ongoing clinical trials for Parkinson's and Alzheimer's disease, ischemic stroke, glioblastoma multiforme, and multiple sclerosis. Finally, this review discusses prospects for MSC-based therapeutics in the form of biomaterials, as well as the use of electromagnetic fields to enhance MSCs' proliferation and differentiation into neuronal cells.
Collapse
Affiliation(s)
- Jasmina Isaković
- Omnion Research International, Zagreb, Croatia.,Department of Histology and Embryology, University of Zagreb School of Medicine, Zagreb, Croatia
| | - Klara Šerer
- University of Zagreb School of Medicine, Zagreb, Croatia
| | - Barbara Barišić
- University of Zagreb School of Dental Medicine, Zagreb, Croatia
| | - Dinko Mitrečić
- Department of Histology and Embryology, University of Zagreb School of Medicine, Zagreb, Croatia.,Laboratory for Stem Cells, Croatian Institute for Brain Research, University of Zagreb School of Medicine, Zagreb, Croatia
| |
Collapse
|
|
7
|
Zang R, Barth A, Wong H, Marik J, Shen J, Lade J, Grove K, Durk MR, Parrott N, Rudewicz PJ, Zhao S, Wang T, Yan Z, Zhang D. Design and Measurement of Drug Tissue Concentration Asymmetry and Tissue Exposure-Effect (Tissue PK-PD) Evaluation. J Med Chem 2022; 65:8713-8734. [PMID: 35790118 DOI: 10.1021/acs.jmedchem.2c00502] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
The "free drug hypothesis" assumes that, in the absence of transporters, the steady state free plasma concentrations equal to that at the site of action that elicit pharmacologic effects. While it is important to utilize the free drug hypothesis, exceptions exist that the free plasma exposures, either at Cmax, Ctrough, and Caverage, or at other time points, cannot represent the corresponding free tissue concentrations. This "drug concentration asymmetry" in both total and free form can influence drug disposition and pharmacological effects. In this review, we first discuss options to assess total and free drug concentrations in tissues. Then various drug design strategies to achieve concentration asymmetry are presented. Last, the utilities of tissue concentrations in understanding exposure-effect relationships and translational projections to humans are discussed for several therapeutic areas and modalities. A thorough understanding in plasma and tissue exposures correlation with pharmacologic effects can provide insightful guidance to aid drug discovery.
Collapse
Affiliation(s)
- Richard Zang
- IDEAYA Biosciences, South San Francisco, California 94080, United States
| | - Aline Barth
- Global Blood Therapeutics, South San Francisco, California 94080, United States
| | - Harvey Wong
- The University of British Columbia, Vancouver, BC V6T 1Z3, Canada
| | - Jan Marik
- Genentech, South San Francisco, California 98080, United States
| | - Jie Shen
- AbbVie, Irvine, California 92612, United States
| | - Julie Lade
- Amgen Inc., South San Francisco, California 94080, United States
| | - Kerri Grove
- Novartis, Emeryville, California 94608, United States
| | - Matthew R Durk
- Genentech, South San Francisco, California 98080, United States
| | - Neil Parrott
- Roche Innovation Centre, Basel CH-4070, Switzerland
| | | | | | - Tao Wang
- Coherus BioSciences, Redwood City, California 94605, United States
| | - Zhengyin Yan
- Genentech, South San Francisco, California 98080, United States
| | - Donglu Zhang
- Genentech, South San Francisco, California 98080, United States
| |
Collapse
|
|
8
|
Vicinanza C, Lombardi E, Da Ros F, Marangon M, Durante C, Mazzucato M, Agostini F. Modified mesenchymal stem cells in cancer therapy: A smart weapon requiring upgrades for wider clinical applications. World J Stem Cells 2022; 14:54-75. [PMID: 35126828 PMCID: PMC8788179 DOI: 10.4252/wjsc.v14.i1.54] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Revised: 08/06/2021] [Accepted: 12/23/2021] [Indexed: 02/06/2023] Open
Abstract
Mesenchymal stem stromal cells (MSC) are characterized by the intriguing capacity to home toward cancer cells after systemic administration. Thus, MSC can be harnessed as targeted delivery vehicles of cytotoxic agents against tumors. In cancer patients, MSC based advanced cellular therapies were shown to be safe but their clinical efficacy was limited. Indeed, the amount of systemically infused MSC actually homing to human cancer masses is insufficient to reduce tumor growth. Moreover, induction of an unequivocal anticancer cytotoxic phenotype in expanded MSC is necessary to achieve significant therapeutic efficacy. Ex vivo cell modifications are, thus, required to improve anti-cancer properties of MSC. MSC based cellular therapy products must be handled in compliance with good manufacturing practice (GMP) guidelines. In the present review we include MSC-improving manipulation approaches that, even though actually tested at preclinical level, could be compatible with GMP guidelines. In particular, we describe possible approaches to improve MSC homing on cancer, including genetic engineering, membrane modification and cytokine priming. Similarly, we discuss appropriate modalities aimed at inducing a marked cytotoxic phenotype in expanded MSC by direct chemotherapeutic drug loading or by genetic methods. In conclusion, we suggest that, to configure MSC as a powerful weapon against cancer, combinations of clinical grade compatible modification protocols that are currently selected, should be introduced in the final product. Highly standardized cancer clinical trials are required to test the efficacy of ameliorated MSC based cell therapies.
Collapse
Affiliation(s)
- Carla Vicinanza
- Stem Cell Unit, Centro di Riferimento Oncologico di Aviano, IRCCS, Aviano 33081, Italy
| | - Elisabetta Lombardi
- Stem Cell Unit, Centro di Riferimento Oncologico di Aviano, IRCCS, Aviano 33081, Italy
| | - Francesco Da Ros
- Stem Cell Unit, Centro di Riferimento Oncologico di Aviano, IRCCS, Aviano 33081, Italy
| | - Miriam Marangon
- Stem Cell Unit, Centro di Riferimento Oncologico di Aviano, IRCCS, Aviano 33081, Italy
| | - Cristina Durante
- Stem Cell Unit, Centro di Riferimento Oncologico di Aviano, IRCCS, Aviano 33081, Italy
| | - Mario Mazzucato
- Stem Cell Unit, Centro di Riferimento Oncologico di Aviano, IRCCS, Aviano 33081, Italy
| | - Francesco Agostini
- Stem Cell Unit, Centro di Riferimento Oncologico di Aviano, IRCCS, Aviano 33081, Italy
| |
Collapse
|
|
9
|
Feng H, Yang X, Zhang L, Liu Q, Feng Y, Wu D, Liu Y, Yang J. Mannose-Modified Chitosan Poly(lactic- co-glycolic acid) Microspheres Act as a Mannose Receptor-Mediated Delivery System Enhancing the Immune Response. Polymers (Basel) 2021; 13:polym13132208. [PMID: 34279352 PMCID: PMC8271610 DOI: 10.3390/polym13132208] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Revised: 06/26/2021] [Accepted: 06/30/2021] [Indexed: 12/16/2022] Open
Abstract
The mannose receptor (MAN-R)-targeted delivery system is commonly used to deliver antigens to macrophages or immature dendritic cells (DCs) to promote the efficiency of antigen presentation. To maximize the enhancement effects of chitosan (CS) and induce an efficient humoral and cellular immune response against an antigen, we encapsulated ovalbumin (OVA) in poly(lactic-co-glycolic acid) (PLGA) microspheres (MPs) and conjugated it with MAN-modified CS to obtain MAN-R-targeting nano-MPs (MAN-CS-OVA-PLGA-MPs). The physicochemical properties, drug loading rate, and immunomodulation activity of MAN-CS-OVA-PLGA-MPs were evaluated. In vitro, MAN-CS-OVA-PLGA-MPs (80 μg mL−1) could enhance the proliferation of DCs and increase their phagocytic efficiency. In vivo, MAN-CS-OVA-PLGA-MPs significantly increased the ratio of CD3+CD4+/CD3+CD8+ T cells, increased CD80+, CD86+, and MHC II expression in DCs, and improved OVA-specific IgG, IgG1, IgG2a, and IgG2b antibodies. Moreover, MAN-CS-OVA-PLGA-MPs promoted cytokine (IFN-γ, IL-4, and IL-6) production in mice. Taken together, our results show that MAN-CS-OVA-PLGA-MPs may act by activating the T cells to initiate an immune response by promoting the maturation of dendritic cells and improving their antigen presentation efficiency. The current study provides a basis for the use of MAN-CS-OVA-PLGA-MPs as an antigen and adjuvant delivery system targeting the MAN-R on the surface of macrophages and dendritic cells.
Collapse
Affiliation(s)
- Haibo Feng
- College of Animal Husbandry and Veterinary Medicine, Southwest Minzu University, Chengdu 610041, China; (X.Y.); (L.Z.); (Q.L.); (Y.F.); (D.W.)
- Key Laboratory of Ministry of Education and Sichuan Province for Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization, Chengdu 610041, China
- Correspondence: ; Tel./Fax: +86-28-85522310
| | - Xiaonong Yang
- College of Animal Husbandry and Veterinary Medicine, Southwest Minzu University, Chengdu 610041, China; (X.Y.); (L.Z.); (Q.L.); (Y.F.); (D.W.)
- Key Laboratory of Ministry of Education and Sichuan Province for Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization, Chengdu 610041, China
| | - Linzi Zhang
- College of Animal Husbandry and Veterinary Medicine, Southwest Minzu University, Chengdu 610041, China; (X.Y.); (L.Z.); (Q.L.); (Y.F.); (D.W.)
- Key Laboratory of Ministry of Education and Sichuan Province for Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization, Chengdu 610041, China
| | - Qianqian Liu
- College of Animal Husbandry and Veterinary Medicine, Southwest Minzu University, Chengdu 610041, China; (X.Y.); (L.Z.); (Q.L.); (Y.F.); (D.W.)
- Key Laboratory of Ministry of Education and Sichuan Province for Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization, Chengdu 610041, China
| | - Yangyang Feng
- College of Animal Husbandry and Veterinary Medicine, Southwest Minzu University, Chengdu 610041, China; (X.Y.); (L.Z.); (Q.L.); (Y.F.); (D.W.)
- Key Laboratory of Ministry of Education and Sichuan Province for Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization, Chengdu 610041, China
| | - Daiyan Wu
- College of Animal Husbandry and Veterinary Medicine, Southwest Minzu University, Chengdu 610041, China; (X.Y.); (L.Z.); (Q.L.); (Y.F.); (D.W.)
- Key Laboratory of Ministry of Education and Sichuan Province for Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization, Chengdu 610041, China
| | - Yunjie Liu
- Department of Veterinary Medicine, Southwest University, Rongchang 402460, China; (Y.L.); (J.Y.)
| | - Jie Yang
- Department of Veterinary Medicine, Southwest University, Rongchang 402460, China; (Y.L.); (J.Y.)
| |
Collapse
|