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Inducing Optimal Antitumor Immune Response through Coadministering iRGD with Pirarubicin Loaded Nanostructured Lipid Carriers for Breast Cancer Therapy.
- Source :
-
Molecular pharmaceutics [Mol Pharm] 2017 Jan 03; Vol. 14 (1), pp. 296-309. Date of Electronic Publication: 2016 Dec 12. - Publication Year :
- 2017
-
Abstract
- Chemotherapeutic agents trigger antitumor immune response through inducing immunogenic tumor cell death. However, severe toxicity to immune system and insufficient immunogenic cell death hinder chemotherapy from arousing efficient antitumor immunity in vivo. In this study, the cytotoxic drug, pirarubicin (THP), was entrapped into nanostructured lipid carriers (NLC); THP-NLC significantly reduced the toxicity of THP to immune system and improved immune status of breast cancer bearing mice. When THP-NLC was coinjected with iRGD (a tumor-penetrating peptide), drug accumulation in tumors was greatly elevated, which led to significant control of tumor growth and increase of immunogenic tumor cell death. Subsequently, the cytotoxic T lymphocytes (CD3 <superscript>+</superscript> and CD8 <superscript>+</superscript> cells) infiltration and cytokine (IFN-γ and INF-α) secretion in tumors were heavily increased. The efficient T-cell dependent control of tumors in the late stage and the lower side effects contributed to the longest whole survival of THP-NLC + iRGD treated mice. Therefore, the coadministration of THP-NLC with iRGD resulted in increased tumor cell direct-killing death and enhanced antitumor immune response. Our results illustrated that THP could serve as an immunogenic cell death inducer and the proposed drug delivery strategy might impact cancer immunotherapy by arousing increased immunogenic tumor cell death.
- Subjects :
- Adjuvants, Pharmaceutic administration & dosage
Adjuvants, Pharmaceutic chemistry
Animals
Antineoplastic Agents administration & dosage
Antineoplastic Agents chemistry
Breast Neoplasms metabolism
Cell Line, Tumor
Doxorubicin administration & dosage
Drug Carriers chemistry
Drug Delivery Systems methods
Female
Lipids chemistry
Male
Mice
Mice, Inbred BALB C
Oligopeptides chemistry
Rats
Rats, Sprague-Dawley
T-Lymphocytes, Cytotoxic drug effects
Breast Neoplasms drug therapy
Doxorubicin analogs & derivatives
Drug Carriers administration & dosage
Immunity drug effects
Lipids administration & dosage
Nanostructures administration & dosage
Oligopeptides administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 1543-8392
- Volume :
- 14
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Molecular pharmaceutics
- Publication Type :
- Academic Journal
- Accession number :
- 27936775
- Full Text :
- https://doi.org/10.1021/acs.molpharmaceut.6b00932