Carrier-Free Nanomedicine for Cancer Immunotherapy

Abstract

With the rapid development of nanotechnology, carrier-based nano-drug delivery systems (DDSs) have been widely studied due to their advantages in optimizing pharmacokinetic and distribution profiles. However, despite those merits, some carrier-related limitations, such as low drug-loading capacity, systematic toxicity and unclear metabolism, usually prevent their further clinical transformation. Carrier-free nanomedicines with non-therapeutic excipients, are considered as an excellent paradigm to overcome these obstacles, owing to their superiority in improving both drug delivery efficacy and safety concern. In recent years, carrier-free nanomedicines have opened new horizons for cancer immunotherapy, and have already made outstanding progress. Herein, in this review, we are focusing on making an integrated and exhaustive overview of lately reports about them. Firstly, the major synthetic strategies of carrier-free nanomedicines are introduced, such as nanocrystals, prodrug-, amphiphilic drug-drug conjugates (ADDCs)-, polymer-drug conjugates-, and peptide-drug conjugates (PepDCs)-assembled nanomedicines. Afterwards, the typical applications of carrier-free nanomedicines in cancer immunotherapy are well-discussed, including cancer vaccines, cytokine therapy, enhancing T-cell checkpoint inhibition, as well as modulating tumor microenvironment (TME). After that, both the advantages and the potential challenges, as well as the future prospects of carrier-free nanomedicines in cancer immunotherapy, were discussed. And we believe that it would be of great potential practiced and reference value to the relative fields.

Biomaterials Elicit Pyroptosis Enhancing Cancer Immunotherapy

“…[132] They can be obtained using various preparation methods, but their usage must be optimized by considering their advantages, such as large surface area and high biocompatibility, and disadvantages, such as high preparation difficulty, low stability, and potential toxicity. [133] Li et al [104] developed a…”

“…[ 132 ] They can be obtained using various preparation methods, but their usage must be optimized by considering their advantages, such as large surface area and high biocompatibility, and disadvantages, such as high preparation difficulty, low stability, and potential toxicity. [ 133 ] Li et al. [ 104 ] developed a chemo‐photodynamic nanoplatform(A‐C/NPs) that effectively induced GSDME‐mediated pyroptosis resulting in immunogenic cell death that released HMGB1, ATP, and CRT, showing potent antitumor effects in a breast cancer mouse model and effectively suppressing tumor growth.…”

Calcium Carbonate/Polydopamine Composite Nanoplatform Based on TGF-β Blockade for Comfortable Cancer Immunotherapy

“…Therefore, developing reagents that can effectively eliminate tumors while alleviating cancer pain is crucial for improving patients’ quality of life . In recent years, tumor immunotherapy has been regarded as the most promising therapeutic strategy. − Nevertheless, the inherent immunosuppressive microenvironment of the tumor greatly reduces the effectiveness of the immunotherapy. Therefore, the elimination of immunosuppressive factors is a critical method for immunotherapy. − Transforming growth factor-β (TGF-β), as an immunosuppressive cytokine in the tumor microenvironment, has been shown to promote tumor immune escape and metastasis, making it a critical target for immunotherapy. − Additionally, TGF-β also plays a pivotal role in tumor-induced hyperalgesia. − Therefore, the efficient inhibition of TGF-β within the tumor extracellular matrix can mitigate tumor-induced immunosuppression and alleviate cancer-associated pain.…”

Self‐Assembled Amphiphilic Camptothecin Nanoparticles with Glutathione‐Responsive and Tumor‐Targeting Ability for Enhanced Colorectal Cancer Therapy

“…[8] Carrier-free nanodrugs with high drug-loading efficiency (50%-100%) have attracted interest in the research community. [9] Camptothecin and its analogs, which contain planar pentacyclic quinolones and have a high tendency to self-assemble into cylindrical aggregates in water. However, it is difficult to form stable nanoparticles (NPs) using single-free CPT.…”