Biomaterial Database

Co-delivery of doxorubicin and interleukin-2 via chitosan based nanoparticles for enhanced antitumor efficacy. 2017

Jingjing Wu, and Cui Tang, and Chunhua Yin

State Key Laboratory of Genetic Engineering, Department of Pharmaceutical Sciences, School of Life Sciences, Fudan University, Shanghai 200438, China.

In order to reduce toxicity and improve antitumor therapeutic effects of doxorubicin (DOX) and recombinant human interleukin-2 (rhIL-2), we developed a hydrophilic cationic polymer (N,N,N-trimethyl chitosan, TMC) based nanocomplexes (FTCD/rhIL-2) which could efficiently mediate systemic co-delivery of hydrophobic DOX and water-soluble rhIL-2 to achieve the purpose of combination therapy. DOX was covalently conjugated to TMC through cis-aconitic anhydride (CA) which endowed nanocomplexes a pH-sensitive release of DOX, while rhIL-2 was loaded through electrostatic adsorption without compromise of bioactivity. The resultant nanocomplexes exhibited sub-spherical shape (∼200nm) and positive charge (>20mV). Folate (FA) modification was utilized with the intention of active targeting, which was however correlated with weakened tumor growth inhibition, emphasizing the importance of balance in overcoming diverse delivery barriers for efficacious antitumor therapy. Compared with free drugs, FTCD/rhIL-2 nanocomplexes significantly delayed tumor growth, increased the serum immunoglobulin G (IgG) level and the amount of tumor infiltrated cytotoxic T lymphocytes. These results indicated that the combinational administration of DOX and rhIL-2 based on polymer nanoparticles could serve as an effective strategy in antitumor therapy. Combined administration of doxorubicin (DOX) and recombinant human interleukin-2 (rhIL-2) has been utilized for the treatment of tumors. However the traditional administration brought to severe side effects, and the efficiency of current delivery systems were unsatisfactory. Herein we developed a hydrophilic cationic polymer based nanoparticle delivery system which facilitated simultaneous and systemic co-delivery of hydrophobic DOX and water-soluble rhIL-2. This system achieved pH-sensitive release of DOX and sustained release of rhIL-2 in vitro, meanwhile, improved anti-tumor efficacy and reduced side-effect in vivo. Thus, our study provided a solution for combinational administration of DOX and rhIL-2 and could serve as an effective strategy in antitumor therapy.

UI	MeSH Term	Description	Entries
D007111	Immunity, Cellular	Manifestations of the immune response which are mediated by antigen-sensitized T-lymphocytes via lymphokines or direct cytotoxicity. This takes place in the absence of circulating antibody or where antibody plays a subordinate role.	Cell-Mediated Immunity,Cellular Immune Response,Cell Mediated Immunity,Cell-Mediated Immunities,Cellular Immune Responses,Cellular Immunities,Cellular Immunity,Immune Response, Cellular,Immune Responses, Cellular,Immunities, Cell-Mediated,Immunities, Cellular,Immunity, Cell-Mediated,Response, Cellular Immune
D007376	Interleukin-2	A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes.	IL-2,Lymphocyte Mitogenic Factor,T-Cell Growth Factor,TCGF,IL2,Interleukin II,Interleukine 2,RU 49637,RU-49637,Ro-23-6019,Ro-236019,T-Cell Stimulating Factor,Thymocyte Stimulating Factor,Interleukin 2,Mitogenic Factor, Lymphocyte,RU49637,Ro 23 6019,Ro 236019,Ro236019,T Cell Growth Factor,T Cell Stimulating Factor
D002470	Cell Survival	The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.	Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D004317	Doxorubicin	Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.	Adriamycin,Adriablastin,Adriablastine,Adriblastin,Adriblastina,Adriblastine,Adrimedac,DOXO-cell,Doxolem,Doxorubicin Hexal,Doxorubicin Hydrochloride,Doxorubicin NC,Doxorubicina Ferrer Farm,Doxorubicina Funk,Doxorubicina Tedec,Doxorubicine Baxter,Doxotec,Farmiblastina,Myocet,Onkodox,Ribodoxo,Rubex,Urokit Doxo-cell,DOXO cell,Hydrochloride, Doxorubicin,Urokit Doxo cell
D004705	Endocytosis	Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. ENDOSOMES play a central role in endocytosis.	Endocytoses
D005260	Female		Females
D005492	Folic Acid	A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses (POACEAE). Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia.	Pteroylglutamic Acid,Vitamin M,Folacin,Folate,Folic Acid, (D)-Isomer,Folic Acid, (DL)-Isomer,Folic Acid, Calcium Salt (1:1),Folic Acid, Monopotassium Salt,Folic Acid, Monosodium Salt,Folic Acid, Potassium Salt,Folic Acid, Sodium Salt,Folvite,Vitamin B9,B9, Vitamin
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D000970	Antineoplastic Agents	Substances that inhibit or prevent the proliferation of NEOPLASMS.	Anticancer Agent,Antineoplastic,Antineoplastic Agent,Antineoplastic Drug,Antitumor Agent,Antitumor Drug,Cancer Chemotherapy Agent,Cancer Chemotherapy Drug,Anticancer Agents,Antineoplastic Drugs,Antineoplastics,Antitumor Agents,Antitumor Drugs,Cancer Chemotherapy Agents,Cancer Chemotherapy Drugs,Chemotherapeutic Anticancer Agents,Chemotherapeutic Anticancer Drug,Agent, Anticancer,Agent, Antineoplastic,Agent, Antitumor,Agent, Cancer Chemotherapy,Agents, Anticancer,Agents, Antineoplastic,Agents, Antitumor,Agents, Cancer Chemotherapy,Agents, Chemotherapeutic Anticancer,Chemotherapy Agent, Cancer,Chemotherapy Agents, Cancer,Chemotherapy Drug, Cancer,Chemotherapy Drugs, Cancer,Drug, Antineoplastic,Drug, Antitumor,Drug, Cancer Chemotherapy,Drug, Chemotherapeutic Anticancer,Drugs, Antineoplastic,Drugs, Antitumor,Drugs, Cancer Chemotherapy