Responsive polymeric drug delivery systems for combination anticancer therapy: experimental design and computational insights

Abstract

Combination therapy has been designed to overcome the setbacks of traditional chemotherapy in anticancer therapy. Since combination therapy comprises a combination of anticancer agents, the different pharmacokinetics and biodistribution properties of multiple drugs are the primary concern. Stimuli-responsive polymers can vary in structure with changes in environmental conditions. Therefore, the microenvironmental differences between tumor sites and normal tissues can be utilized to achieve controlled drug release within a specific time and location range. Thus, stimuli-responsive polymers have the ability to optimize combination drug administration. This present review addresses four different strategies for preparing a polymeric combination drug delivery system. Different types of payloads, including various chemo drugs, gene drugs, and photosensitizers, that have been explored in the experiment are crucial parts of the discussion in this review. In addition, the triggering conditions of stimuli-responsive polymers used in combination therapy in recent years are summarized. Moreover, due to the investigation of drug-carrier or drug-drug interactions at the molecular level, computational chemistry provides inspiration for the rational design of novel drug delivery systems. Thus, a series of simulations to calculate the thermodynamic and kinetic properties of drug carriers are also introduced. The challenges and perspectives of nanocarrier-based combination therapy have also been discussed.

Graphical Abstract

Keywords:

• Combination therapy
• computational chemistry
• polymer-drug conjugates
• rational design
• stimuli-responsive

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Additional information

Funding

This research received funding from the National Natural Science Foundation of China [Grant Nos.: 21978047, 21776046, 21606043], the Fundamental Research Funds for the Central Universities [Grant No.: 2242020K40033], and the Six Talent Peaks Project in Jiangsu Province [Grant No. XCL-079].