Abstract
Insufficient transport of therapeutic cargo into tumor bed is a bottleneck in cancer nanomedicine. Block copolymers are promising carriers with smaller particle size by ratio modification. Here, we constructed cisplatin nanoparticles with sizes ranging from 8 to 40 nm to study the permeability and therapy of Lewis lung carcinoma. We synthesized methoxypoly(ethylene glycol)2000-block poly(L-glutamic acid sodium salt)1979 loading cisplatin through complexation reaction. The cisplatin nanomedicine has high drug loading and encapsulation efficiency. In vitro data demonstrated that cisplatin nanoparticles had equivalent growth-inhibiting effects on Lewis lung carcinoma cells compared to free cisplatin. In vivo evidences showed cisplatin nanoparticles had superior antitumor effects on the Lewis lung carcinoma mouse model with no obvious side effects. All results indicated that optimizing the ratio of block copolymers to obtain smaller sized nanomedicine could act as a promising strategy for overcoming the inadequate accumulation in poorly vascularized tumors.
Highlights
Nonspecific distribution and inadequate accumulation of therapeutic cargo are the main challenges in nanomedicine (Poon et al, 2020)
Methoxypoly(ethylene glycol) (MPEG, Mn 2000, Aldrich, United States), γ-benzyl-L-glutamate-N-carboxy anhydride (BLGNCA), dichloromethane, pyridine, P-toluene sulfonyl chloride (TsCl), absolute ether, ammonium hydroxide, benzene, dimethylsulfoxide (DMSO) and 1,4-dioxane were purchased from Sinopharm Chemical Reagent Co., Ltd. (Shanghai, China)
The deprotection of the benzyl group was performed by mixing with 0.025 N NaOH at ambient temperature to obtain MPEG2000-P(Glu), the peak of which at δ 5.034 and 7.256 ppm disappeared, confirming the complete deprotection (Figure 5B)
Summary
Nonspecific distribution and inadequate accumulation of therapeutic cargo are the main challenges in nanomedicine (Poon et al, 2020). The high activity of the chloride ion as the leaving group leads to considerable nephrotoxicity and neurotoxicity, as well as other adverse reactions, resulting in limited clinical application (Ghosh, 2019). For this reason, in the subsequent design of platinum-based drugs, the chloride ion was replaced with the relatively stable cyclobutanecarboxylic acid and glycolic acid, respectively, to derive carboplatin (Calvert et al, 1982) and nedaplatin (Kuwahara et al, 2010). The commercial introduction of next-generation platinum drugs has been followed by a new challenge of high levels
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