Intracellular tracking of drug release from pH-sensitive polymeric nanoparticles via FRET for synergistic chemo-photodynamic therapy

Abstract

BackgroundSynergistic therapy of tumor is a promising way in curing cancer and in order to achieve effective tumor therapy with real-time drug release monitoring, dynamic cellular imaging and antitumor activity.ResultsIn this work, a polymeric nanoparticle with Forster resonance energy transfer (FRET) effect and chemo-photodynamic properties was fabricated as the drug vehicle. An amphiphilic polymer of cyclo(RGDfCSH) (cRGD)-poly(ethylene glycol) (PEG)-Poly(l-histidine) (PH)-poly(ε-caprolactone) (PCL)-Protoporphyrin (Por)-acting as both a photosensitizer for photodynamic therapy (PDT) and absorption of acceptor in FRET was synthesized and self-assembled into polymeric nanoparticles with epirubicin (EPI)-acting as an antitumor drug for chemotherapy and fluorescence of donor in FRET. Spherical EPI-loaded nanoparticles with the average size of 150 ± 2.4 nm was procured with negatively charged surface, pH sensitivity and high drug loading content (14.9 ± 1.5%). The cellular uptake of EPI-loaded cRGD-PEG-PH-PCL-Por was monitored in real time by the FRET effect between EPI and cRGD-PEG-PH-PCL-Por. The polymeric nanoparticles combined PDT and chemotherapy showed significant anticancer activity both in vitro (IC50 = 0.47 μg/mL) and better therapeutic efficacy than that of free EPI in vivo.ConclusionsThis work provided a versatile strategy to fabricate nanoassemblies for intracellular tracking of drug release and synergistic chemo-photodynamic therapy.

Multifunctional TPP-PEG-biotin self-assembled nanoparticle drug delivery-based combination therapeutic approach for co-targeting of GRP78 and lysosome

“…The Ru-1 may have high affinity to TPP-PEG-biotin during the self-assembly process due to the hydrophobic and π–π stacking interactions [ 17 ]. An interesting feature of π–π stacking interactions is that the interaction forces are affected by environmental conditions such as pH and redox potential [ 18 – 21 ]. In addition, the π–π stacking interactions is very weak compared to the covalent bonding.…”

“…Combination therapy based on chemo drugs has been achieved by different methods. For example, co-delivery of multiple chemo drugs [26,27], antibody-drug conjugates (ADC) [28], small molecule drug conjugates (SMDCs) [29], and combination of photosensitizer with chemo drugs [18,30,31] for targeted cancer therapy have been developed. The combination of two chemo drugs such as docetaxel and prednisone was the first treatment for prostate cancer (PCA).…”

“…In addition, the π-π stacking interactions is very weak compared to the covalent bonding. The pH is a major parameter that affects the release of the π-π stacked drug from the drug loaded self-assembled nanoparticle system [18]. The Ru-1 in Ru-1@TPP-PEG-biotin SANs is thought to stably bind to TPP via the hydrophobic and π-π interaction under the neutral pH condition.…”

“…In vitro release study of Ru-1 loaded TPP-PEG-biotin SANs were performed by the dialysis method as reported previously [18,21]. Dialysis was done by using Spectra/ Por ® Dialysis membrane (molecular cut-off 12-14 KDa) against PBS as release medium.…”

Zinc Sulfide-Based Hybrid Exosome-Coated Nanoplatform for Targeted Treatment of Glioblastoma in an Orthotopic Mouse Glioblastoma Model

“…Fluorescence resonance energy transfer (FRET) and protein assay were carried out for the confirmation of hybridization between liposome and hybrid exosome. [32] Energy transfer in FRET liposome was monitored before and after hybridization as depicted in Fig. 5a.…”