Self-Adaptive Nanomaterials for Rational Drug Delivery in Cancer Therapy

CONSPECTUS: Cancer is a disease characterized by uncontrolled growth and division of abnormal cells, which could be effectively suppressed by various therapeutic agents in clinics. With the increasing knowledge of cancer, the rapid development of different therapeutic agents, such as small molecule cytotoxic drugs, nucleic acids, proteins/peptides, immunomodulators, and so forth, has expanded the modalities of cancer therapy. However, their clinical application is still hampered by the low tumor specificity when applied in vivo. The irrational distribution in healthy tissues may cause severe side effects and reduce the therapeutic effect. Undoubtedly, achieving the on-demand release of therapeutic agents at the tumor site is critical for effective anticancer efficacies with reduced side effects. Benefiting from the development of nanotechnology, nanomaterials are widely exploited to significantly boost the specificity of drugs to the tumor tissue and simultaneously decrease the toxic effects on the normal tissues, leading to improved therapeutic outcomes. Nevertheless, conventional nanomaterials still have multiple drawbacks, such as poor tumor targeting and unavoidable leakage of therapeutic agents. In this regard, the self-adaptive nanomaterials, which respond to the signal changes emitted from the tumor site, might realize the spatiotemporally and quantitatively specific release of drugs. Self-adaptive nanomaterials exhibited capabilities of self-regulation and self-feedback, whose properties, such as charge, size, and shape, underwent an on-demand transformation in response to specific stimuli. Compared to the conventional ones, self-adaptive nanomaterials successfully decrease the frequency of drug release doses within normal tissues and maintain drug concentrations in the tumor cells for a more extended period, thus promoting rational This Account highlights recent developments in the field of self-adaptive nanomaterials used for rational drug delivery in cancer therapy, primarily based on progress made by our group. We discuss self-adaptive nanomaterials responding to endogenous and exogenous stimuli to trigger the release of therapeutic agents in the therapeutic targets of cancer. Chemical approaches used in the construction of self-adaptive nanomaterials and representative examples of recently developed nanomaterials are reviewed, and multistimuli-responsive nanomaterials, addressing the shortcomings of single stimulus-responsive nanomaterials, are also discussed. In addition, we provide a summary of ongoing clinical trials involving self-adaptive nanomaterials in cancer therapy. Finally, we provide an overview of the issues encountered during the transition of these materials from research settings to clinical use. The exploration and optimization of nanomaterial chemical design is an ongoing process. It is hoped that the insights provided in this Account will be a valuable reference for creating the next generation of these promising self-adaptive nanomaterials.