Controlled release of cisplatin from pH-thermal dual responsive nanogels.
In this study, a pH-thermal dual responsive nanogel was applied for cisplatin (CDDP) delivery. CDDP was loaded into the nanogels via conjugation with the carboxyl groups in the nanogels. The conjugation was confirmed by FTIR and XPS. The bonding between CDDP and COOH can be broken by the H(+) or Cl(-). We found that the CDDP released much faster at more acidic environment. The Cl(-) concentration in the human body is about 95-105 mm. The conjugated bond could be easily attacked by Cl(-) while the nanosystem is injected into the body. In order to diminish the Cl(-) triggering release of CDDP from the nanogels, we introduced a thermal-responsive units-NIPAm into the nanogel structure. After NIPAm introduced, the CDDP released much slower from the nanogels at 37 °C in pH = 7.38 buffer in the present of Cl(-) (150 mm) than that without NIPAm. And the CDDP also released slower from the nanogels at 37 °C than at 25 °C. By in vitro release behavior studying, we found that CDDP release from the NIPAm containing nanogels can be accelerated by H(+) attacking and reduced by temperature arising. By cellular uptake observation, we found that the nanogels were mainly localized in the cytoplasm of the cancer cells. The CDDP-loaded nanogels exhibited longer circulation time in vivo while compared to free CDDP. And it has better anti-cancer performance than free CDDP in vivo therapy of breast cancer in mice model. Furthermore, some side effects of CDDP, such as renal toxicity, phlebitis, bone marrow suppression etc. have also been reduced by nanogels loading. The in vitro and in vivo results demonstrated that the dual responsible nanogel is a suitable CDDP delivery candidate.
State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, PR China.
Jinrong
J
Peng
Tingting
T
Qi
Jinfeng
J
Liao
Bingyang
B
Chu
Qian
Q
Yang
Wenting
W
Li
Ying
Y
Qu
Feng
F
Luo
Zhiyong
Z
Qian
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002945:Cisplatin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D020128:Inhibitory Concentration 50; D061986:MCF-7 Cells; D008297:Male; D000080385:Nanogels; D011092:Polyethylene Glycols / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013696:Temperature
D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D000080385:Nanogels; C413692:polyethylene glycol polyethyleneimine nanogel; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D002945:Cisplatin
Cisplatin; Controlled release; Dual responsive; H(+) triggering; Nanogels; Side effect