Polymeric Co-Delivery Systems in Cancer Treatment: An Overview on Component Drugs' Dosage Ratio Effect

Abstract

Multiple factors are involved in the development of cancers and their effects on survival rate. Many are related to chemo-resistance of tumor cells. Thus, treatment with a single therapeutic agent is often inadequate for successful cancer therapy. Ideally, combination therapy inhibits tumor growth through multiple pathways by enhancing the performance of each individual therapy, often resulting in a synergistic effect. Polymeric nanoparticles prepared from block co-polymers have been a popular platform for co-delivery of combinations of drugs associated with the multiple functional compartments within such nanoparticles. Various polymeric nanoparticles have been applied to achieve enhanced therapeutic efficacy in cancer therapy. However, reported drug ratios used in such systems often vary widely. Thus, the same combination of drugs may result in very different therapeutic outcomes. In this review, we investigated polymeric co-delivery systems used in cancer treatment and the drug combinations used in these systems for synergistic anti-cancer effect. Development of polymeric co-delivery systems for a maximized therapeutic effect requires a deeper understanding of the optimal ratio among therapeutic agents and the natural heterogenicity of tumors.

Keywords: chemotherapy; co-delivery systems; nucleic acid delivery; polymeric nanoparticles; stimuli-sensitive polymers; synergistic effect.

Figure 1

Drug loading in polymeric nanoparticles used as co-delivery systems in cancer treatment.

Figure 2

Folate-modified pH-sensitive co-delivery system of FA-poly(DOX+VER) polymer assembly exhibits obvious pH-sensitivity, high active targeting ability, strong multidrug resistance reversal and the enhanced therapeutic effect. Reproduced with permission from Li et al., Journal of Colloid and Interface; Elsevier, 2016 [83].

Figure 3

MMP-2 and glutathione sensitive polymeric nanoparticles used for co-delivery of DOX and miRNA-34a. Reproduced with permission from Salzano et al., Small; John Wiley and sons, 2016 [48]. * p ≤ 0.05, **** p ≤ 0.0001, n = 3, error bars represent mean ± SD.

Figure 4

Co-delivery of DOX and PCT in polymeric nanoparticles consist of P105 and Pluronic F127 into MCF7/ADR cells. Reproduced with permission from Chen et al., International Journal of Pharmaceutics; Elsevier, 2015 [117].

Figure 5

Co-delivery of DOX and pDNA in cationic polymeric nanoparticles with co-localization of cargos and enhanced tumor cell growth inhibition. Reproduced with permission from Chen et al., Polymers; MDPI, 2019 under the license CC BY 4.0 [173].

Figure 6

Schematic structure of mixed dendrimer micelles composed of PAMAM-PEG2k-DOPE and PEG5k-DOPE in co-delivery of DOX and siMDR-1. Reproduced with permission from Pan et al., European Journal of Pharmaceutics and Biopharmaceutics; Elsevier, 2019 [91].