Surface modulation of polymeric nanocarriers enhances the stability and delivery of proteins and small molecules.
OBJECTIVE
We aimed to enhance the stability and therapeutic efficiency of protein-based therapeutic formulations.


METHODS
Proteins were immobilized on the surface of nanoparticles (NPs) to improve both protein stability and protein function, especially enzymatic activity. The modularity of the platform was demonstrated by coating proteins of varied molecular weights and functionalities on the surface of poly(lactic-co-glycolic acid)-based NPs.


RESULTS
Coating proteins to the particle surface greatly enhanced the stability of the NPs, preventing particle aggregation and improving enzymatic potency, including in vivo. Specifically, coating of collagenase I to the particle surface greatly improved the ability of the enzyme to degrade tumor collagen relative to free enzyme, thereby increasing the penetration of adjuvant chemotherapy (doxorubicin). Additionally, the protein coating reduced the rate of doxorubicin release, enabling sustained release of the small-molecule payload.


CONCLUSIONS
The straightforward procedure described herein permits the formulation of modular NPs that can combine and sustain the benefits of small molecules and biologics.
Department of Cancer Immunology & Virology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.|Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA 02114, USA.
Zohreh
Z
Amoozgar
Department of Cancer Immunology & Virology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Michael S
MS
Goldberg
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D017252:CD3 Complex / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival; D017024:Chemotherapy, Adjuvant; D003094:Collagen / Q000378:metabolism; D017364:Collagenases / Q000737:chemistry*; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D064593:Heterografts; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007211:Indoles / Q000737:chemistry; D019344:Lactic Acid / Q000737:chemistry*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry; D013499:Surface Properties; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D047368:Tumor Burden
D000970:Antineoplastic Agents; D017252:CD3 Complex; D004337:Drug Carriers; D007211:Indoles; D011108:Polymers; C568283:polydopamine; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; D004317:Doxorubicin; D003094:Collagen; D017364:Collagenases; C417249:collagenase 1
PLGA; drug delivery; nanoparticle; proteins; small molecules; stability