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A novel delivery system for cisplatin was constructed based on electrostatics-mediated assemblies of gold nanoclusters and PEGylated cationic peptide (cisplatin@GC-pKs). Encapsulated cisplatin in the as-formed micelle like assemblies was observed to demonstrate improved cellar uptake and enhanced chemotherapeutic efficiency in the cisplatin-resistant lung cancer cells. In vivo assays further confirmed that cisplatin@GC-pKs had profound anti-tumor efficiency due to deep penetration and accumulation of nanoscale cisplatin@GC-pKs via the enhanced permeability and retention (EPR) effect at tumor tissues. The constructed cisplatin@GC-pKs in this work demonstrated enhanced anti-tumor activity for lung cancer therapy, as well as a potential treatment strategy for a variety of cisplatin-resistance related malignancies.

Delivery and accumulation of therapeutic drugs into neoplastic cells distant from tumor vessels is a major challenge for antitumor therapy. Herein, we introduced a de novo peptide, p12 (QGSRRRNTVDDWISRRRALC), to conjugate onto the surface of doxorubicin (DOX) and indocyanine green (ICG) co-encapsulated nanoscale liposomes (pLipo-DOX–ICG). The p12 peptide triggered specific binding to CXC chemokine receptor 4 (CXCR4), leading to enhanced cellular uptake and improved accumulation of pLipo-DOX–ICG in CXCR4-overexpressing cancer cells. Moreover, the introduction of ICG molecules endowed pLipo-DOX–ICG with photothermal-induced structural disruption, which may be helpful for the precise and controllable release of doxorubicin at tumor tissue sites in vivo. With these advantages, the constructed pLipo-DOX–ICG demonstrated active targeting behavior for delivery and release of chemotherapeutic drugs, thereby showing much enhanced metastasis inhibition and antitumor efficacy than either drug-containing liposomes without p12 modification or free drugs in breast cancer bearing mice models. Overall, pLipo-DOX–ICG with low toxicity is expected to be a potential therapeutic agent to improve clinical benefits of breast cancer therapies, as well as treatment of a variety of CXCR4-overexpressing malignancies.

Lymph node metastases in cancer patients are associated with high aggressiveness, poor prognosis, and short survival time. The chemokine receptor 4 (CXCR4)/stroma derived factor 1α (CXCL12) biological axis plays a critical role in the spread of cancer cells. Designing effective delivery systems that can successfully deliver CXCR4 antagonists to lymph nodes, which are rich in CXCR4-overexpressing cancer cells, for controlling cancer metastasis remain challenging. In this study, we demonstrated that such a challenge may be alleviated by developing nanometer-sized polyethylene glycol-phosphatidylethanolamine (PEG-PE) micelles for the co-delivery of the CXCR4 antagonistic peptide E5 and doxorubicin (M-E5-Dox). This nanomicelle platform enables the preferential accumulation of cargos into lymph nodes and thus can better inhibit cancer metastasis and enhance antitumor efficacy than either free drugs or single drug-loaded micelles in breast cancer-bearing mouse models. Hence, M-E5-Dox is expected to be a potential therapeutic agent that would improve the clinical benefits of breast cancer therapy and treatment of various CXCR4-overexpressing malignancies.

Acute myeloid leukemia (AML) is the most common adult acute leukemia with very low survival rate due to drug resistance and high relapse rate. The C-X-C chemokine receptor 4 (CXCR4) is highly expressed by AML cells, actively mediating chemoresistance and reoccurrence. Herein, a chemically synthesized CXCR4 antagonistic peptide E5 is fabricated to micelle formulation (M-E5) and applied to refractory AML mice, and its therapeutic effects and pharmacokinetics are investigated. Results show that M-E5 can effectively block the surface CXCR4 in leukemic cells separated from bone marrow (BM) and spleen, and inhibit the C-X-C chemokine ligand 12-mediated migration. Subcutaneous administration of M-E5 significantly inhibits the engraftment of leukemic cells in spleen and BM, and mobilizes residue leukemic cells into peripheral blood, reducing organs' burden and significantly prolonging the survival of AML mice. M-E5 can also increase the efficacy of combining regime of homoharringtonine and doxorubicin. Ribonucleic acid sequencing demonstrates that the therapeutic effect is contributed by inhibiting proliferation and enhancing apoptosis and differentiation, all related to the CXCR4 signaling blockade. M-E5 reaches the concentration peak at 2 h after administration with a half-life of 14.5 h in blood. In conclusion, M-E5 is a novel promising therapeutic candidate for refractory AML treatment.

Correction for ‘Improving the inhibitory effect of CXCR4 peptide antagonist in tumor metastasis with an acetylated PAMAM dendrimer’ by Changliang Liu et al., RSC Adv., 2018, 8, 39948–39956.