Vivek K Pawar1,2, Yuvraj Singh1,2, Komal Sharma1,2, Arpita Shrivastav1, Abhisheak Sharma2,3, Akhilesh Singh4, Jaya Gopal Meher1, Pankaj Singh1,2, Kavit Raval1,2, Himangshu K Bora5, Dipak Datta4, Jawahar Lal3, Manish K Chourasia6,7. 1. Pharmaceutics Division, CSIR-Central Drug Research Institute, Lucknow, U.P, 226031, India. 2. Academy of Scientific & Innovative Research,, New Delhi, 110025, India. 3. Pharmacokinetics & Metabolism Division, CSIR-Central Drug Research Institute, Lucknow, U.P, 226031, India. 4. Biochemistry Division, CSIR-Central Drug Research Institute, Lucknow, U.P, 226031, India. 5. Laboratory Animals Facility, CSIR-Central Drug Research Institute, Lucknow, U.P, 226031, India. 6. Pharmaceutics Division, CSIR-Central Drug Research Institute, Lucknow, U.P, 226031, India. manish_chourasia@cdri.res.in. 7. Academy of Scientific & Innovative Research,, New Delhi, 110025, India. manish_chourasia@cdri.res.in.
Abstract
OBJECTIVE: To utilize nanoparticles produced by condensation of zymosan (an immunotherapeutic polysaccharide) with pegylated polyethylenimine (PEG-PEI) for dual intervention in breast cancer by modulating tumor microenvironment and direct chemotherapy. METHOD: Positively charged PEG-PEI and negatively charged sulphated zymosan were utilized for electrostatic complexation of chemoimmunotherapeutic nanoparticles (ChiNPs). ChiNPs were loaded with doxorubicin hydrochloride (DOX) for improved delivery at tumor site and were tested for in-vivo tolerability. Biodistribution studies were conducted to showcase their effective accumulation in tumor hypoxic regions where tumor associated macrophages (TAMs) are preferentially recruited. RESULTS: ChiNPs modulated TAMs differentiation resulting in decrement of CD206 positive population. This immunotherapeutic action was furnished by enhanced expression of Th1 specific cytokines. ChiNPs also facilitated an anti-angiogenetic effect which further reduces the possibility of tumor progression and metastasis.
OBJECTIVE: To utilize nanoparticles produced by condensation of zymosan (an immunotherapeutic polysaccharide) with pegylated polyethylenimine (PEG-PEI) for dual intervention in breast cancer by modulating tumor microenvironment and direct chemotherapy. METHOD: Positively charged PEG-PEI and negatively charged sulphated zymosan were utilized for electrostatic complexation of chemoimmunotherapeutic nanoparticles (ChiNPs). ChiNPs were loaded with doxorubicin hydrochloride (DOX) for improved delivery at tumor site and were tested for in-vivo tolerability. Biodistribution studies were conducted to showcase their effective accumulation in tumor hypoxic regions where tumor associated macrophages (TAMs) are preferentially recruited. RESULTS: ChiNPs modulated TAMs differentiation resulting in decrement of CD206 positive population. This immunotherapeutic action was furnished by enhanced expression of Th1 specific cytokines. ChiNPs also facilitated an anti-angiogenetic effect which further reduces the possibility of tumor progression and metastasis.
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