Surface Modification of Polymeric Nanoparticles with M2pep Peptide for Drug Delivery to Tumor-Associated Macrophages

Abstract

Purpose: Tumor-associated macrophages (TAMs) with immune-suppressive M2-like phenotype constitute a significant part of tumor and support its growth, thus making an attractive therapeutic target for cancer therapy. To improve the delivery of drugs that control the survival and/or functions of TAMs, we developed nanoparticulate drug carriers with high affinity for TAMs. Methods: Poly(lactic-co-glycolic acid) nanoparticles were coated with M2pep, a peptide ligand selectively binding to M2-polarized macrophages, via a simple surface modification method based on tannic acid-iron complex. The interactions of M2pep-coated nanoparticles with macrophages of different phenotypes were tested in vitro and in vivo. PLX3397, an inhibitor of the colony stimulating factor-1 (CSF-1)/CSF-1 receptor (CSF-1R) pathway and macrophage survival, was delivered to B16F10 tumors via M2pep-modified PLGA nanoparticles. Results: In bone marrow-derived macrophages polarized to M2 phenotype, M2pep-coated nanoparticles showed greater cellular uptake than those without M2pep. Consistently, M2pepcoated nanoparticles showed relatively high localization of CD206 + macrophages in B16F10 tumors. PLX3397 encapsulated in M2pep-coated nanoparticles attenuated tumor growth better than the free drug counterpart. Conclusion: These results support that M2pep-coating can help nanoparticles to interact with M2-like TAMs and facilitate the delivery of drugs that control the tumor-supportive functions of TAMs.

Self-assembled nanofibrils from RGD-functionalized cellulose nanocrystals to improve the performance of PEI/DNA polyplexes

“…The concept of coating an existing nanoparticle system is not new. However, most rely on natural or synthetic polymers that essentially conform to the shape of the nanoparticle without significant changes in the surface morphology [47][48][49][50]. CNCs may provide a new way of coating that not only alter surface chemistries, but also the surface topography of nanoparticles, and hence also their interaction with biological systems [25,26].…”

Nanomedicine-based drug delivery towards tumor biological and immunological microenvironment

“…Pang et al. 172 developed PLGA nanoparticles that were coated with M2-macrophages binding peptide (M2pep) to encapsulate PLX3397, a receptor tyrosine kinase inhibitor that was shown to deplete macrophages in tumors 173 . Results showed an increased uptake of M2pep-coated PLGA nanoparticles in M2-TAMs and reduced tumor growth in a mouse melanoma model.…”

Harnessing nanomedicine to overcome the immunosuppressive tumor microenvironment

“…To increase the selectivity of TAM targeting, Yeo et al developed polymeric NPs coated with M2pep (YEQDPWGVKWWY) that preferentially binds to murine M2-like TAMs via an adhesive layer of tannic acid-Fe 3+ complex (pTA) on the NP surface ( Fig. 6) [119]. M2pep-coated NP-pTA (NP-pTA-M2pep) showed increased cellular uptake by M2-polarized bone marrow-derived macrophages in vitro and CD206 + macrophages in B16F10 melanoma in vivo compared with that of uncoated-NPs, indicating enhanced binding affinity of M2pep-coated NPs.…”

“…Scale bars: 300 μm: (left) free PLX3397-treated tumor composed of sheets of neoplastic epithelial cells with scattered foci of necrosis and hemorrhage; (center) PLX3397@NP-pTA-Al-treated tumor composed of neoplastic epithelial cells with a central core of necrosis expanded by fibroblasts, fibrin, and hemorrhage; (right) PLX3397@NP-pTA-M2pep-treated tumor composed of coalescing bands of necrosis composed of eosinophilic fibrillar material, erythrocytes, and a mixed inflammatory population. Adapted from REF [ 119 ] with permission by Springer Nature. …”