Nanoparticle-based drug delivery systems targeting cancer cell surfaces

Abstract

Traditional cancer chemotherapy easily produces serious toxic and side effects due to the lack of specific selection of tumor cells, which restricts its curative effect. Targeted delivery can increase the concentration of drugs in the target site and reduce their toxic and side effects on normal tissues and cells. Biocompatible and surface-modifiable nanocarriers are novel drug delivery systems, which are used to specifically target tumor sites in a controllable way. One of the effective ways to design effective targeting nanocarriers is to decorate with functional ligands, which can bind to specific receptors overexpressed on the surfaces of cancer cells. Various functional ligands, including transferrin, folic acid, polypeptide and hyaluronic acid, have been widely explored to develop tumor-selective drug delivery systems. This review focuses on the research progress of various receptors overexpressed on the surfaces of cancer cells and different nano-delivery systems of anticancer drugs targeted on the surfaces of cancer cells. We believe that through continuous research and development, actively targeted cancer nano-drugs will make a breakthrough and become an indispensable platform for accurate cancer treatment.

Fig. 1. (A) Normal tissues maintain vascular integrity by peripheral cells and lymphatic vessels exist. (B) The tumor tissue contains defective blood vessels, many cystic structures and perforations, and lymphatic vessels are lacking. Reprinted with permission from ref. . Copyright @2010 Elsevier.

Fig. 2. Mechanism of action of folate and the folate receptor against the tumor. Reprinted with permission from ref. . Copyright @2015 Spring Nature.

Fig. 3. The mechanism of tyrosine kinase inhibitors and anti-EGFR monoclonal antibodies. Reprinted with permission from ref. . Copyright @2021 Elsevier.

Fig. 4. (A) Schematic illustration of the EGFR-targeting nanoparticle SQ90 NPs-Pep for photoacoustic NIR-II fluorescence dual-modality imaging-guided PTT of oral cancer; (B) cellular uptake (CAL 27 and L-02 cells) of Rho B-labeled NPs observed by CSLM; (C) semiquantitative analysis of relative fluorescent intensity at different time points after various treatments; (D) tumor volume growth of mice with CAL 27 tumors in each group. Reprinted with permission from ref. . Copyright @2022 Springer Nature.

Fig. 5. Preparation method of CD44-Doxil and therapeutic effect in vivo and in vitro. Reprinted with permission from ref. . Copyright @2015 Elsevier.

Fig. 6. (a) Construction of the dual-functional dendrimer-based drug carrier and (b) schematic illustration of tumor targeting therapy using the dual-functional drug delivery system. Reprinted with permission from ref. . Copyright @2019 The Royal Society of Chemistry.

Fig. 7. (A) Preparation and mechanism diagram of Au-C225-p53DNA; (B) confocal uptake of Au-C225-p53DNA in SK-OV-3 cells (top) and CHO cells (bottom). Reprinted with permission from ref. . Copyright @2019 American Chemical Society.

Fig. 8. Schematic diagram of the preparation of GNR–HA–ALA/Cy7.5-HER2, and its application in HER2/CD44 dual-targeting and fluorescence imaging-guided PDT/PTT combination therapy for breast cancer. Reprinted with permission from ref. . Copyright @2019 Elsevier.

Fig. 9. Schematic illustration of DOX-loaded MSN–DOX@PDA–PEG–FA. Reprinted with permission from ref. . Copyright @2017 American Chemical Society.

Fig. 10. Schematic structure of MSN-SS-HA/DOX drug delivery and cumulative release profiles of MSN-SS-HA/DOX and MSN-SH/DOX in pH 5.0 PBS under different conditions. Reprinted with permission from ref. . Copyright @2015 Elsevier.

Fig. 11. (a) The synthesis and surface coating of SPIONs and FA-SPIONs. (b) The DOX loaded FA-SPIONs for FA-mediated and magnetically targeted drug delivery to the tumor and the MR imaging. Reprinted with permission from ref. . Copyright @2017 Elsevier.