Chemical conjugation mitigates immunotoxicity of chemotherapy via reducing receptor-mediated drug leakage from lipid nanoparticles.

Immunotoxicity remains a major hindrance to chemotherapy in cancer therapy. Nanocarriers may alleviate the immunotoxicity, but the optimal design remains unclear. Here, we created two variants of maytansine (DM1)-loaded synthetic high-density lipoproteins (D-sHDL) with either physically entrapped (ED-sHDL) or chemically conjugated (CD-sHDL) DM1. We found that CD-sHDL showed less accumulation in the tumor draining lymph nodes (DLNs) and femur, resulting in a lower toxicity against myeloid cells than ED-sHDL via avoiding scavenger receptor class B type 1 (SR-B1)-mediated DM1 transportation into the granulocyte-monocyte progenitors and dendritic cells. Therefore, higher densities of lymphocytes in the tumors, DLNs, and blood were recorded in mice receiving CD-sHDL, leading to a better efficacy and immune memory of CD-sHDL against colon cancer. Furthermore, liposomes with conjugated DM1 (CD-Lipo) showed lower immunotoxicity than those with entrapped drug (ED-Lipo) through the same mechanism after apolipoprotein opsonization. Our findings highlight the critical role of drug loading patterns in dictating the biological fate and activity of nanomedicine.

Recent Progress in the Design and Application of Supramolecular Peptide Hydrogels in Cancer Therapy.

Supramolecular peptide hydrogel (SPH) is a class of biomaterials self-assembled from peptide-based gelators through non-covalent interactions. Among many of its biomedical applications, the potential of SPH in cancer therapy has been vastly explored in the past decade, taking advantage of its good biocompatibility, multifunctionality, and injectability. SPHs can exert localized cancer therapy and induce systemic anticancer immunity to prevent tumor recurrence, depending on the design of SPH. This review first gives a brief introduction to SPH and then outlines the major types of peptide-based gelators that have been developed so far. The methodologies to tune the physicochemical properties and biological activities are summarized. The recent advances of SPH in cancer therapy as carriers, prodrugs, or drugs are highlighted. Finally, the clinical translation potential and main challenges in this field are also discussed.