Tailoring carrier-free nanocombo of small-molecule prodrug for combinational cancer therapy

The outcomes of monotherapy could not satisfy clinical cancer treatment owing to the challenges of tumor heterogeneity, multi-drug resistance, tumor metastasis and relapse. In response, the significance of combina-tional cancer therapy has been highlighted. Traditional combinational schemes usually utilize free drug for multi drug administration, independently. The diverse pharmacokinetics and biodistribution greatly hinder the antitumor effects and cause systematic toxicity. To tackle the hinderance, various nanoparticulate drug delivery systems (Nano-DDSs) have been developed. However, conventional Nano-DDSs encapsulate drugs into carrier materials through noncovalent interactions, resulting in low drug loading, fixed multi drug encapsulation ratio, chemical instability and carrier-associated toxicity. Recently, carrier-free nanocombos based on self-assembling small-molecule prodrugs (SPNCs) have emerged as a versatile Nano-DDSs for multiple drug delivery. Benefited by the self-assembly capability, SPNCs could be facilely fabricated with distinct merits of ultra-high drug loading, adjustable drug ratio and negligible carrier-associated toxicity. Herein, we summarize the latest trends of SPNCs. First, a basic review on self-assembling small-molecule prodrugs is presented. Additionally, facile techniques to prepare SPNCs are introduced. Furthermore, advanced combinational therapies based on SPNCs are spotlighted with special emphasis on synergistic mechanisms. Finally, future prospects and challenges are discussed.

Automated summary

Monotherapy is not sufficient for clinical cancer treatment due to various challenges. Combinational cancer therapy has gained significance to overcome these challenges. Traditional combinatorial schemes using free drugs independently have issues such as diverse pharmacokinetics and biodistribution. To address these issues, carrier-free nanocombos based on self-assembling small-molecule prodrugs (SPNCs) have been developed, offering advantages like high drug loading and adjustable drug ratio with minimal toxicity.