Doxorubicin Hydrochloride Loaded Zymosan-Polyethylenimine Biopolymeric Nanoparticles for Dual ‘Chemoimmunotherapeutic’ Intervention in Breast Cancer

• Published in: Pharmaceutical research Vol. 34; no. 9; pp. 1857 - 1871
• Main Authors: Pawar, Vivek K., Singh, Yuvraj, Sharma, Komal, Shrivastav, Arpita, Sharma, Abhisheak, Singh, Akhilesh, Meher, Jaya Gopal, Singh, Pankaj, Raval, Kavit, Bora, Himangshu K., Datta, Dipak, Lal, Jawahar, Chourasia, Manish K.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.09.2017; Springer; Springer Nature B.V
• Subjects: Animals; Antibiotics, Antineoplastic - administration & dosage; Antibiotics, Antineoplastic - pharmacokinetics; Antibiotics, Antineoplastic - therapeutic use; Biochemistry; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Breast - drug effects; Breast - immunology; Breast - pathology; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - immunology; Breast Neoplasms - pathology; Cancer; Cell Proliferation - drug effects; Chemotherapy; Cytokines; Cytokines - immunology; Development and progression; Doxorubicin; Doxorubicin - administration & dosage; Doxorubicin - pharmacokinetics; Doxorubicin - therapeutic use; Drug Carriers - chemistry; Drug Delivery Systems; Female; Hypoxia; Immunologic Factors - administration & dosage; Immunologic Factors - pharmacokinetics; Immunologic Factors - therapeutic use; Immunotherapy; Lymphocytes T; Macrophages; Macrophages - drug effects; Macrophages - immunology; Medical Law; Metastases; Mice, Inbred BALB C; Nanoparticles; Nanoparticles - chemistry; Pharmacology/Toxicology; Pharmacy; Polyethylene glycol; Polyethyleneimine; Polyethyleneimine - chemistry; Polysaccharides; Research Paper; Static Electricity; Tissue Distribution; Zymosan - administration & dosage; Zymosan - pharmacokinetics; Zymosan - therapeutic use; cytokine; hypoxia; tumor associated macrophages; chemoimmunotherapeutic nanoparticles; angiogenesis
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-017-2195-2

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.