A pH-responsive prodrug delivery system of 10-HCPT for controlled release and tumor targeting

Liu, Yang; Li, Dan; Guo, Xin; Xu, Haiwei; Li, Zhi; Zhang, Yanling; Song, Chuanjun; Fan, Ruhan; Tang, Xing; Zhang, Zhenzhong

doi:10.2147/ijn.s125849

Cited by 15 publications

(8 citation statements)

References 37 publications

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“…It has been reported that the extracellular pH value in most solid tumours is weakly acidic, approximately pH 6.5-7.2, and the intracellular organelles exhibit much lower pH values (pH 4.0-6.5) compared to the pH of 7.4 in normal physiological tissue. Various kinds of pH-responsive polymeric micelles have been developed in recent years [25][26][27][28]. For example, poly(β-amino ester) (PAE) is a type of polycationic polymer which exhibits a reported pK b value of about 6.2 [10,[29][30][31].…”

Section: Introductionmentioning

confidence: 99%

pH-responsive polymeric micelles self-assembled from amphiphilic copolymer modified with lipid used as doxorubicin delivery carriers

Zhou

Jin

et al. 2018

R. Soc. open sci.

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In the present study, a novel pH-responsive amphiphilic copolymer, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)] conjugated poly(β-amino esters) (DSPE-b-PEG-b-PAE-b-PEG-b-DSPE), was designed and successfully synthesized via Michael-type step polymerization. The chemical structure of the pentablock copolymer was confirmed with proton nuclear magnetic resonance (1H-NMR) and Fourier transform infrared (FT-IR) spectroscopy. The copolymer was able to self-assemble into core/shell polymeric micelles in aqueous solution at low concentrations, and its critical micelle concentration (CMC) value was 4.5 mg l−1 determined by fluorescence spectrophotometry. The pKb value of the copolymer was about 6.5, confirmed by acid–base titration, indicating the pH-sensitivity of the polymeric micelle. The hydrodynamic diameter, distribution and zeta potential of the polymeric micelles at different pH conditions were monitored by dynamic light scattering (DLS). Doxorubicin (DOX) was encapsulated into the core of the micelles with a high drug loading content (15.9%) and entrapment efficacy (60.4%). In vitro experiments demonstrated that the release behaviour of DOX from the DOX-loaded polymeric micelles (DOX-PMs) was pH-triggered. When the pH decreased from 7.4 to 5.0, the drug release rate was markedly accelerated. MTT assay showed that the copolymer had negligible cytotoxicity whereas the DOX-PMs displayed high toxicity for tumour cells such as B16F10, HepG2 and HeLa cell lines. The results demonstrated that these pH-sensitive polymeric micelles could be used as potential anti-cancer drug carriers for cancer chemotherapy with controlled release.

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Section: Introductionmentioning

confidence: 99%

pH-responsive polymeric micelles self-assembled from amphiphilic copolymer modified with lipid used as doxorubicin delivery carriers

Zhou

Jin

et al. 2018

R. Soc. open sci.

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“…For PMLA-ami-dOX, dOX release was slower than that of PMLA-Hz-dOX, and there was no pH dependence. Using this polymeric drug design, the conjugates can stably preserve drugs under physiological conditions and selectively degrade and release them by responding to the tumor extracellular pH (pH e ), endosomes (pH 5-6) or lysosomes (pH 4-5) (25,35,36). The in vitro drug release experiments showed that the release of dOX was pH-dependent.…”

Section: Characterization Of Pmla-hz-dox and Pmla-ami-doxmentioning

confidence: 99%

Preparation and biological evaluation of a novel pH-sensitive poly (β-malic acid) conjugate for antitumor drug delivery

Qiao

Peng

et al. 2018

Int J Mol Med

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Poly (β-malic acid), referred to as PMLA, has been synthesized and introduced as a polymeric drug carrier due to its desirable biological properties. In the present study, a novel pH-sensitive polymer-drug conjugate based on PMLA, PMLA-Hz-doxorubicin (dOX), was prepared, and another conjugate, PMLA-ami-dOX, was synthesized as a comparison. The structures, conjugation efficiency, and drug release properties of the prodrugs were determined. The cytotoxicity and cell uptake were assessed using the HT1080 human fibrosarcoma cell line as an in vitro cell model. The release of dOX in the two conjugates were pH-dependent in PBS buffer at a pH of 5.6, 6.0, 6.8 and 7.4. The quantity of drug released increased with the decrease in pH, and PMLA-ami-dOX released twice as much as PMLA-Hz-dOX (12 h). The cytotoxicity of PMLA-Hz-dOX at pH 7.4 was lower than that of free dOX and increased with the decrease in pH, indicating that the cytotoxicity of PMLA-Hz-dOX was pH-sensitive. Flow cytometry and confocal experiments confirmed the efficiency of the PMLA-Hz-dOX conjugate. Therefore, bonding dOX to PMLA via an acid-sensitive hydrazone bond may be used to reduce its toxic side effects on normal tissues while responding to tumor pH and releasing the drug.

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“…The drug is therefore encapsulated into liposomal NPs to deliver the drug to the tumor site via actively targeted NPs, thereby achieving precise drug release. 29 , 30 At the same time, the addition of liquid fluorocarbon to NPs, 31 and it indicated that phase-transformation lipid NPs coated with liquid perfluoropentane (PFP) can elicit liquid-gas phase transition. Using a certain intensity of external ultrasonic irradiation, PFP-coated lipid NPs can be changed into lipid microbubbles to enhance ultrasound imaging.…”

Section: Introductionmentioning

confidence: 99%

iRGD Peptide-Mediated Liposomal Nanoparticles with Photoacoustic/Ultrasound Dual-Modality Imaging for Precision Theranostics Against Hepatocellular Carcinoma

Shi

et al. 2021

IJN

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Purpose Prepare a multifunctional ultrasound molecular probe, cell-penetrating peptide-modified 10-hydroxycamptothecin-loaded phase-transformation lipid nanoparticles (iRGD-ICG-10-HCPT-PFP-NPs), and to combine iRGD-ICG-10-HCPT-PFP -NPs with low-intensity focused ultrasound (LIFU) for precision theranostics against hepatocellular carcinoma (HCC). Materials and Methods The morphology of nanoparticles (NPs) and iRGD-ICG-10-HCPT-PFP-NPs was detected. In vitro, we examined targeting ability by flow cytometry and confocal laser scanning microscopy (CLSM), assessed penetration ability into hepatoma cells, and assessed killing ability. In vivo, we examined the targeting ability of the NPs with a photoacoustic (PA) imager and fluorometer (FL), while LIFU irradiation was used to trigger the release of chemotherapeutic drugs, which had a therapeutic effect on tumors. Results The particle size of iRGD-ICG-10-HCPT-PFP-NPs was 298.4 ± 10.42 nm. In vitro, iRGD-ICG-10-HCPT-PFP-NPs bound more to SK-Hep1 cells than ICG-10-HCPT-PFP-NPs. iRGD-ICG-10-HCPT-PFP-NPs could achieve PA/ultrasound imaging. The percentage of antiproliferative and apoptotic cells in the iRGD-ICG-10-HCPT-PFP-NPs+LIFU group was significantly higher. In vivo, iRGD-ICG-10-HCPT-PFP-NPs can target tumor sites and achieve PA/ultrasound imaging. The tumor volume in the iRGD-ICG-10-HCPT-PFP-NPs+LIFU group was significantly smaller, and the antiproliferative and proapoptotic effects were higher. Conclusion We successfully prepared a novel molecular probe that has good targeting, can perform ultrasound/PA dual-modality imaging, and can penetrate deep into tumors to achieve better therapeutic tumor effects, providing a new idea and method for theranostics of HCC.

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A pH-responsive prodrug delivery system of 10-HCPT for controlled release and tumor targeting

Cited by 15 publications

References 37 publications

pH-responsive polymeric micelles self-assembled from amphiphilic copolymer modified with lipid used as doxorubicin delivery carriers

pH-responsive polymeric micelles self-assembled from amphiphilic copolymer modified with lipid used as doxorubicin delivery carriers

Preparation and biological evaluation of a novel pH-sensitive poly (β-malic acid) conjugate for antitumor drug delivery

iRGD Peptide-Mediated Liposomal Nanoparticles with Photoacoustic/Ultrasound Dual-Modality Imaging for Precision Theranostics Against Hepatocellular Carcinoma

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