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Platinum-Based Nanovectors Engineered with Immuno-Modulating Adjuvant for Inhibiting Tumor growth and Promoting Immunity
- Source :
- Theranostics
- Publication Year :
- 2018
- Publisher :
- Ivyspring International Publisher, 2018.
-
Abstract
- Although there is ample evidence that the chemotherapeutic drugs trigger an immune response, the efficient tumor rejection or regression is not guaranteed probably due to the massive immunosuppression within the tumor microenvironment. Thus, a rational delivery platform that overcomes immunosuppression is needed to maximally achieve both cytotoxic and immune-modulatory functions of chemotherapeutics. Accumulating evidence suggests that platinum-based drugs might be suitable for this application. Methods: The dendrigraft polylysine (DGL) with its uniform size and multifunctional groups was employed as the polymeric core and conjugated with platinum-based compounds as therapeutics and WKYMVm peptide (Wpep) as a targeting ligand to construct the novel delivery platform Wpep-DGL/Pt. A series of in vitro and in vivo analyses, including physical and chemical characterizations, targeting property, biosafety, and antitumor efficacy of Wpep-DGL/Pt were systematically carried out. Results: Wpep-DGL/Pt showed potent antitumor efficacy in MDA-MB-231 cells tumor-bearing nude mice with a deficient immune system, demonstrating targeted delivery of chemotherapeutics and the resultant cytotoxicity. Furthermore, in immunocompetent mice bearing 4T1 cells tumors, Wpep-DGL/Pt activated immune cells and induced cell death proving their dual function of chemotherapeutic and immunomodulatory efficacy. Conclusion: This work represents a novel approach for cancer immunotherapy by integrating nanotechnology and platinum-based therapeutics which not only efficiently exerts the chemotherapeutic cytotoxic effect on tumor cell but also restores immune response of immunological cells within the tumor microenvironment.
- Subjects :
- 0301 basic medicine
Drug Compounding
medicine.medical_treatment
Mice, Nude
Medicine (miscellaneous)
Antineoplastic Agents
chemotherapy
immune response
Mice
03 medical and health sciences
Drug Delivery Systems
Immune system
Adjuvants, Immunologic
Cancer immunotherapy
In vivo
Neoplasms
Tumor Microenvironment
medicine
Animals
Cytotoxic T cell
Polylysine
platinum
Cytotoxicity
Pharmacology, Toxicology and Pharmaceutics (miscellaneous)
tumor immune microenvironment
Mice, Inbred BALB C
Tumor microenvironment
Chemistry
Immunosuppression
Immunity, Humoral
030104 developmental biology
Cancer research
Nanoparticles
Female
Immunotherapy
Peptides
Adjuvant
Research Paper
Subjects
Details
- ISSN :
- 18387640
- Volume :
- 8
- Database :
- OpenAIRE
- Journal :
- Theranostics
- Accession number :
- edsair.doi.dedup.....e0767ccbe77035ad2027615a2da5e90a