Colloidal Assemblies Composed of Polymeric Micellar/Emulsified Systems Integrate Cancer Therapy Combining a Tumor-Associated Antigen Vaccine and Chemotherapeutic Regimens

Abstract

Integrative medicine comprising a tumor-associated antigen vaccine and chemotherapeutic regimens has provided new insights into cancer therapy. In this study, the AB-type diblock copolymers poly(ethylene glycol)–polylactide (PEG–PLA) were subjected to the dispersion of poorly water-soluble molecules in aqueous solutions. The physicochemical behavior of the chemotherapeutic agent DBPR114 in the PEG–PLA-polymeric aqueous solution was investigated by dynamic light scattering (DLS) technology. In vitro cell culture indicated that replacing the organic solvent DMSO with PEG–PLA polymeric micelles could maintain the anti-proliferative effect of DBPR114 on leukemia cell lines. A murine tumor-associated antigen vaccine model was established in tumor-bearing mice to determine the effectiveness of these formulas in inducing tumor regression. The results demonstrated that the therapeutic treatments effectively reinforced each other via co-delivery of antitumor drug/antigen agents to synergistically integrate the efficacy of cancer therapy. Our findings support the potential use of polymeric micellar systems for aqueous solubilization and expansion of antitumor activity intrinsic to DBPR114 and tumor-associated antigen therapy.

A Polylactide-Based Micellar Adjuvant Improves the Intensity and Quality of Immune Response

“…Regarding the quality of the immune response, the micelles induced Abs with a high avidity compared to the gold standards and were again similar to that of 160 nm-PLA NP. One hypothetical explanation of this strong humoral response with high avidity could be related to the B Cell Receptor (BCR) engagement due to the biodistribution profile of micelles through the draining lymph system, favoring a BCR clustering, as it has been observed with other self-assembled micelles [47,48] and NP [49,50]. To date, to our knowledge, no micellar-based system has shown a performance that can compete with vaccine gold standards (alum and MF59) by means of both intensity and quality of humoral immune response.…”