PLGA-Rhodamine/PLGA from PolySciTech used in development of peptide-targeted nanoparticles to macrophages for cancer therapy

Cancer is not a homogenous mass of cells, rather it is a complex mixture of microenvironment and tissue. Several factors of the microenvironment act to promote the growth of the cancer tumor. One of these is the presence of tumor-associated macrophages (immune cells) which promote the growth of cancer cells by suppressing the local immune system as well as by other mechanisms. One target for cancer therapy is to prevent the mechanisms of these support cells thereby leaving cancer more vulnerable and reducing its growth and survival. Recently, researchers at Purdue University and Soochow University (China) used PLGA (AP031) and fluorescent PLGA-Rhodamine (AV011) from PolySciTech (www.polyscitec.com) to develop peptide-bound nanoparticles with selective uptake towards these macrophages. The fluorescent PLGA enables tracking the location of the nanoparticles as a means to confirm uptake. This research holds promise for the development of powerful and selective therapies against cancer. Read more: Pang, Liang, Yihua Pei, Gozde Uzunalli, Hyesun Hyun, L. Tiffany Lyle, and Yoon Yeo. "Surface Modification of Polymeric Nanoparticles with M2pep Peptide for Drug Delivery to Tumor-Associated Macrophages." Pharmaceutical Research 36, no. 4 (2019): 65. https://link.springer.com/article/10.1007/s11095-019-2596-5

“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, M2pep-coated 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. KEY WORDS: Drug delivery M2pep PLGA nanoparticles PLX3397 tumor-associated macrophages”

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