Co-delivery of docetaxel and bortezomib based on a targeting nanoplatform for enhancing cancer chemotherapy effects

Abstract

Using facile polydopamine (PDA)-based surface modification and a pH-sensitive catechol-boronate binding mechanism, a novel drug delivery system was designed for the treatment of breast cancer. The system was able to achieve the following goals: active targeting, pH responsiveness, in vivo blood circulation for a prolonged period of time, and dual drug loading. After coating with PDA, the docetaxel (DTX)-loaded star-shaped copolymer cholic acid-poly(lactide-co-glycolide) nanoparticles (CA-PLGA@PDA/NPs) were functionalized with amino-poly(ethylene glycol)-folic acid (NH-PEG-FA) and bortezomib (BTZ) to form the targeting composition, DTX-loaded CA-PLGA@PDA-PEG-FA + BTZ/NPs. The novel NPs exhibited similar drug release characteristics compared to unfunctionalized CA-PLGA/NPs. Meanwhile, the incorporated NH-PEG-FA contributed to active targeting which was illustrated by cellular uptake experiments and biodistribution studies. Moreover, the pH responsive binding between BTZ and PDA was demonstrated to be effective to release BTZ at the tumor acidic environment for synergistic action with DTX. Both in vitro cytotoxicity and in vivo antitumor studies demonstrated that the novel nanoplatform exhibited the most suitable therapeutic effects. Taken together, the versatile PDA modified DTX-loaded CA-PLGA@PDA-PEG-FA + BTZ/NPs offered a promising chemotherapeutic strategy for enhancing breast cancer treatment.

pH-Responsive Dual Drug-Loaded Nanocarriers Based on Poly (2-Ethyl-2-Oxazoline) Modified Black Phosphorus Nanosheets for Cancer Chemo/Photothermal Therapy

“…Additionally, the appropriate size and narrow size distribution may be beneficial to NSs accumulation in tumors through the EPR effect (Torchilin, 2011). Besides, the zeta potential of bare BP NSs was -18.9 mV, while that after surface modification with PDA became -16.6 mV, probably because phenolic hydroxyl groups on the PDA layer were deprotonated at neutral pH (Cheng et al, 2017c; Nie et al, 2017). After NH 2 -PEOz and NH 2 -PEG modification, the zeta potentials of BP@PDA-PEOz and BP@PDA-PEG in deionized water were measured to be -10.5 mV and -13.2 mV, respectively.…”

“…Under identical conditions, photothermal-triggered drug release was tested at pH 5.0 with 6 min of 808 nm laser irradiation at the power density of 1.0 W cm -2 . In vitro BTZ release and photothermal-triggered drug release from BP-DOX@PDA-PEOz-BTZ NSs were detected by LC 1200 HPLC system (Nie et al, 2017) (Agilent Technologies, Santa Clara, CA, United States). Compounds were separated by a reverse-phase C18 column (5 μm, 150 × 4.6 mm; Agilent Technologies, Santa Clara, CA, United States) using a mobile phase comprising deionized water and acetonitrile (20/80 for BTZ, v/v).…”

“…Conventionally, the in vivo circulation of nanocarriers is prolonged through surface modification with hydrophilic or zwitterionic polymers among which polyethylene glycol (PEG) is most investigated and utilized due to excellent biocompatibility and hydrophilicity, especially for the polymers based drug delivery (Chen et al, 2017a; Feng et al, 2017; Guo et al, 2018; Wang et al, 2018). This technique is also known as PEGylation (Zeng et al, 2013; Cheng et al, 2017c; Nie et al, 2017; Zhao et al, 2017; Xiao et al, 2018; Tang et al, 2019). However, it suffers from the following issues.…”

Polydopamine-Functionalized CA-(PCL-ran-PLA) Nanoparticles for Target Delivery of Docetaxel and Chemo-photothermal Therapy of Breast Cancer

“…Nano-biotechnology has shown promising prospects for changing the landscape of pharmaceutical and biomedical industries fundamentally ( Shi et al, 2010 ; Tao et al, 2015b , 2017b , d ; He et al, 2016 ; Wang et al, 2016 , 2017 ; Hofmann et al, 2017 ; Niu et al, 2017 ; Qi et al, 2017 ; Shi B. et al, 2017 ; Shi J. et al, 2017 ; Xu et al, 2017a , b ). The key to solve the side effects caused by cytotoxic anticancer drugs is to increase the local effective drug concentrations in the tumor sites, which could be addressed by employing polymeric nanoparticles (NPs) as highly promising target drug delivery systems ( Kamaly et al, 2016 ; Kakkar et al, 2017 ; Nie et al, 2017 ; Tao et al, 2017c ; Xu et al, 2017 ). In addition, due to the molecular complexity of cancers, treatment based on monotherapies is suboptimal and can not effective eliminated tumors ( Greco and Vicent, 2009 ; Sun et al, 2011 ).…”

<p>pH-Responsive Artesunate Polymer Prodrugs with Enhanced Ablation Effect on Rodent Xenograft Colon Cancer</p>

“…39 As aforementioned, the ζ potentials of the prodrugs increased significantly by decreasing the surrounding pH from 7.4 to 6.5 ( Figure S4B), due to the protonation of the PBAE segment, and subsequent partial charge neutralization. 40,41 The stability of the polymer prodrugs was investigated by measurement of micelles' sizes vs incubation time according to our previous protocol. 35 As shown in Figure S5, the sizes of PELA-PBAE-ART2 prodrug showed high stability in the investigated period, whereas the sizes of other prodrugs increased to some extent during incubation.…”