Design of Nanodrug Delivery Systems for Tumor Bone Metastasis.

Tumor metastasis is a complex process that is controlled at the molecular level by numerous cytokines. Primary breast and prostate tumors most commonly metastasize to bone, and the development of increasingly accurate targeted nanocarrier systems has become a research focus for more effective anti-bone metastasis therapy. This review summarizes the molecular mechanisms of bone metastasis and the principles and methods for designing bone-targeted nanocarriers and then provides an in-depth review of bone-targeted nanocarriers for the treatment of bone metastasis in the context of chemotherapy, photothermal therapy, gene therapy, and combination therapy. Furthermore, this review also discusses the treatment of metastatic and primary bone tumors, providing directions for the design of nanodelivery systems and future research.

Enzyme-Induced Shape-Shifting Peptide Nanocarrier Coloaded with Paclitaxel and Dipyridamole Inhibits Platelet Function and Tumor Metastasis.

Tumor-associated platelets can bind to tumor cells and protect circulating tumor cells from NK-mediated immune surveillance. Tumor-associated platelets secrete cytokines to induce the epithelial-mesenchymal transition (EMT) in tumor cells, which promotes tumor metastasis. Combining chemotherapeutic agents with antiplatelet drugs can reduce the occurrence of metastasis, but the systemic application of chemotherapeutic agents and antiplatelet drugs is prone to causing serious side effects. Therefore, delivering drugs to the tumor microthrombus site for long-lasting inhibition is a problem that needs to be addressed. Here, we show that small molecule peptide nanoparticles containing the Cys-Arg-Glu-Lys-Ala (CREKA) peptide can deliver the platelet inhibitor dipyridamole (DIP) and the chemotherapeutic drug paclitaxel (PTX) to tumor tissues, thereby inhibiting tumor-associated platelet function while killing tumor cells. The drug-loaded nanoparticles PD/Pep1 inhibited platelet-tumor cell interactions, were effectively taken up by tumor cells, and underwent morphological transformation induced by alkaline phosphatase (ALP) to prolong the retention time of the drugs. After intravenous injection, PD/Pep1 can target tumors and inhibit tumor metastasis. Thus, this small molecule peptide nanoformulation provides a simple strategy for efficient drug delivery and shows promise as a novel cancer therapy platform.

A dual drug-loaded peptide system with morphological transformation prolongs drug retention and inhibits breast cancer growth.

The treatment of breast cancer relies heavily on chemotherapy, but chemotherapy is limited by the disadvantages of poor targeting, susceptibility to extracellular matrix (ECM) interference and a short duration of action in tumor cells. To address these limitations, we developed an amphipathic peptide containing an RGD motif, Pep1, that encapsulated paclitaxel (PTX) and losartan potassium (LP) to form the drug-loaded peptide PL/Pep1. PL/Pep1 self-assembled into spherical nanoparticles (NPs) under normal physiological conditions and transformed into aggregates containing short nanofibers at acidic pH. The RGD peptide facilitated tumor targeting and the aggregates prolonged drug retention in the tumor, which allowed more drug to reach and accumulate in the tumor tissue to promote apoptosis and remodel the tumor microenvironment. The results of in vitro and in vivo experiments confirmed the superiority of PL/Pep1 in terms of targeting, prolonged retention and facilitated penetration for antitumor therapy. In conclusion, amphipathic peptides as coloaded drug carriers are a new platform and strategy for breast cancer chemotherapy.