Abstract

For enhanced anti-cancer performance, human serum albumin fragments (HSAFs) nanoparticles (NPs) were developed as paclitaxel (PTX) carrier in this paper. Human albumins were broken into fragments via degradation and crosslinked by genipin to form HSAF NPs for better biocompatibility, improved PTX drug loading and sustained drug release. Compared with crosslinked human serum albumin NPs, the HSAF-NPs showed relative smaller particle size, higher drug loading, and improved sustained release. Cellular and animal results both indicated that the PTX encapsulated HSAF-NPs have shown good anti-cancer performance. And the anticancer results confirmed that NPs with fast cellular internalization showed better tumor inhibition. These findings will not only provide a safe and robust drug delivery NP platform for cancer therapy, but also offer fundamental information for the optimal design of albumin based NPs.

Highlights

  • To figure out how physical and chemical properties of NPs may affect the cellular behavior of human serum albumin fragments (HSAFs) NPs, a HSAF NP platform was prepared using genipin as crosslinker with different crosslinking degrees and sizes, but similar surface charge

  • A HSAF NP system with controllable crosslinking density and size were developed for better biosafety and anticancer efficacy

  • The HSAF NP library with a series of crosslinking degrees and particle sizes were developed, and the results showed that the similar particle size of HSAF NPs had different crosslinking densities, and the highest crosslinking density combined with the smallest particle size

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Summary

Introduction

With the fast growing of material chemistry and nanomedicine, biodegradable nanoscale drug delivery platforms, including nanoparticles, micelles (Wang et al, 2014a; Li W. et al, 2016; Qu et al, 2017) and liposomes, have been widely utilized for biomedical diagnosis (Park et al, 2009; Morral-Ruiz et al, 2013; Wang et al, 2014b; Hu et al, 2018) and therapy (Boussif et al, 1995; Ding et al, 2013; Xing et al, 2013; Bertrand et al, 2014; You et al, 2016; Ge et al, 2017; Li et al, 2017; Pan et al, 2018; Yang et al, 2018). Even the nanoparticles (NPs) based on FDA approved materials, such as the poly-ε-caprolactone (PCL), poly(DL-lactic acid), poly(lactide-cocaprolactone), and poly(lactideco-glycolide) (PLGA), are still toxic for high dosage treatment (Singh and Ramarao, 2013). As a biodegradable, non-toxic and non-immunogenic protein, has been used to prepare NPs (Elzoghby et al, 2012). The crosslinked albumin NPs were able to increase their physical stabilities, but

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