Reversing multi-drug tumor resistance to Paclitaxel by well-defined pH-sensitive amphiphilic polypeptide block copolymers via induction of lysosomal membrane permeabilization

Mostoufi, Hassan; Yousefi, Gholamhossein; Tamaddon, Ali Mohammad; Firuzi, Omidreza

doi:10.1016/j.colsurfb.2018.10.072

Cited by 23 publications

(9 citation statements)

References 65 publications

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“…Hence, it can be expected that pHis and pLeu will have a synergic effect on lysosomal disruption and subsequent cellular trafficking of PTX. It is noteworthy that we observed the same results with PEG-polyglutamate-polyleucine (PEG-PGA-PLeu) copolymer which consisted of a polyacid (PGA) instead of polybase (pHis) in the induction of LMP (Mostoufi, Yousefi, Tamaddon, & Firouzi, 2019). Considering the fact that PGA cannot cause proton sponge effect, points us to the critical role of pLeu as LMP inducer.…”

Section: Discussionsupporting

confidence: 78%

“…Therefore, a combined mechanism can be considered the induction of LMP by pHPMA 5kD ‐pHis 5kD ‐pLeu 3kD copolymer. Disregarding the exact mechanism, due to the fact that the release of lysosomal proteases into cytosol is lethal for cells through activation of caspase enzymes in an apoptosis‐dependent fashion (Boya & Kroemer, 2008; Mostoufi et al, 2019; Repnik, Česen, & Turk, 2014; Sohaebuddin, Thevenot, Baker, Eaton, & Tang, 2010) and considering abnormalities in cancer cells regarding LMP regulation (Boya & Kroemer, 2008), invention of materials able to induce LMP might open a new window toward cancer therapy.…”

Section: Discussionmentioning

confidence: 99%

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Paclitaxel‐loaded polypeptide‐polyacrylamide nanomicelles overcome drug‐resistance by enhancing lysosomal membrane permeability and inducing apoptosis

Abbasi

Yousefi

Tamaddon

et al. 2020

J Biomedical Materials Res

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The aim of the current project was to investigate the in vitro properties of Paclitaxel (PTX)-loaded pHPMA 5kD-pHis 5kD-pLeu 3kD nanomicelles (NMs) on multidrug resistance cell line. Circular dichroism analysis was done to investigate the effect of pH on the secondary structure of the copolymer. Cytotoxicity assay together with fluorescence imaging and flow cytometry were performed to get an insight about toxicity and cellular uptake mechanism of NMs. Acridine orange assay, rhodamine 123 (Rh123) accumulation assay, and apoptosis analysis were conducted for further

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Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Paclitaxel‐loaded polypeptide‐polyacrylamide nanomicelles overcome drug‐resistance by enhancing lysosomal membrane permeability and inducing apoptosis

Abbasi

Yousefi

Tamaddon

et al. 2020

J Biomedical Materials Res

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“…The fluorescence emission of AO depends on its concentration, so AO exhibits red fluorescence in intact lysosomes at high concentration and green fluorescence in cytosol at low concentration. 34 As shown in Figure 7(A), after fullerenol treatment, the relocation of AO Lysosome maintains an acidic environment of about pH 4.5, which is optimal for enzymatic activity. Thus, the effect of various lysosome inhibitors on lysosome function is realized by altering lysosome pH, such as by using chloroquine (CQ).…”

Section: Resultsmentioning

confidence: 99%

“…AO, a lysosomotropic weak base, can be accumulated in the acidic lysosomal compartment owing to proton trapping. The fluorescence emission of AO depends on its concentration, so AO exhibits red fluorescence in intact lysosomes at high concentration and green fluorescence in cytosol at low concentration . As shown in Figure (A), after fullerenol treatment, the relocation of AO from an intact lysosome to the cytoplasm was detected by a decrease in the red fluorescence, indicating significant LMP.…”

Section: Resultsmentioning

confidence: 99%

Inhibition of Autophagy via Lysosomal Impairment Enhances Cytotoxicity of Fullerenol under Starvation Condition

Yang

Hua

Fan

et al. 2020

ACS Appl. Bio Mater.

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Autophagy is well-known as a common cellular response to nanomaterials. As one of the most comprehensively studied carbon-based nanomaterials, fullerene and its derivatives have been reported to bring about autophagic features in various cell lines, but little is known about the role of fullerenol (C60(OH)44) on the modulation of autophagy in human gastric tumor cell line SGC-7901. Fullerenol treatment led to the accumulation of autophagosomes, as evidenced by the increased fluorescent intensity of monodansylcadaverine (MDC) staining cells, an elevated level of LC3 protein, and the observation of auotphagosomes in cytoplasm. Subsequent results of the p62 level demonstrated that the accumulation of autophagosomes resulted from the blockade of autophagic flux rather than the activation of autophagy. Fullerenol disrupted autophagic flux by impairing lysosomal function, including lysosome membrane permeabilization (LMP), alkaline of lysosomes, and reduced activity of capthesin B. Interestingly, fullerenol treatment was noncytotoxic under a nutrient-rich condition. When serum was deprived, cytotoxicity occurred in a concentration- and time-dependent manner, along with massive vacuoles in cytoplasm, a large amount of ROS generation, and finally cell death, which can be ascribed to the disruption of essential autophagy in cells. Taken together, understanding this autophagy–lysosome pathway will shed light on the potential anticancer application of fullerenol.

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“…Paclitaxel (PTX), a typical tubulin inhibitor that induces mitotic stagnation of tumor cells in the G2 and M stages, has been widely studied in the treatment of cervical and breast cancers [28]. However, resistance to PTX is frequently observed, and is possibly related to an overexpression of P-gp efflux pumps, multidrug resistance (MDR-1) gene, and a high expression of a growth factor, such as platelet-derived growth factor (PDGF) [29][30][31]. Imatinib (IMN), the first tyrosine kinase inhibitor approved for the treatment of chronic myelogenous leukemia and malignant gastrointestinal stromal tumor [32,33], has been reported to inhibit the growth of cervical cancer cells by inhibition of PDGFR and c-kit [34,35].…”

Section: Introductionmentioning

confidence: 99%

Sequential Release of Paclitaxel and Imatinib from Core–Shell Microparticles Prepared by Coaxial Electrospray for Vaginal Therapy of Cervical Cancer

Liu

Chen

et al. 2021

IJMS

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To optimize the anti-tumor efficacy of combination therapy with paclitaxel (PTX) and imatinib (IMN), we used coaxial electrospray to prepare sequential-release core–shell microparticles composed of a PTX-loaded sodium hyaluronate outer layer and an IMN-loaded PLGA core. The morphology, size distribution, drug loading, differential scanning calorimetry (DSC), Fourier transform infrared spectra (FTIR), in vitro release, PLGA degradation, cellular growth inhibition, in vivo vaginal retention, anti-tumor efficacy, and local irritation in a murine orthotopic cervicovaginal tumor model after vaginal administration were characterized. The results show that such core–shell microparticles were of spherical appearance, with an average size of 14.65 μm and a significant drug-loading ratio (2.36% for PTX, 19.5% for IMN, w/w), which might benefit cytotoxicity against cervical-cancer-related TC-1 cells. The DSC curves indicate changes in the phase state of PTX and IMN after encapsulation in microparticles. The FTIR spectra show that drug and excipients are compatible with each other. The release profiles show sequential characteristics in that PTX was almost completely released in 1 h and IMN was continuously released for 7 days. These core–shell microparticles showed synergistic inhibition in the growth of TC-1 cells. Such microparticles exhibited prolonged intravaginal residence, a >90% tumor inhibitory rate, and minimal mucosal irritation after intravaginal administration. All results suggest that such microparticles potentially provide a non-invasive local chemotherapeutic delivery system for the treatment of cervical cancer by the sequential release of PTX and IMN.

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Reversing multi-drug tumor resistance to Paclitaxel by well-defined pH-sensitive amphiphilic polypeptide block copolymers via induction of lysosomal membrane permeabilization

Cited by 23 publications

References 65 publications

Paclitaxel‐loaded polypeptide‐polyacrylamide nanomicelles overcome drug‐resistance by enhancing lysosomal membrane permeability and inducing apoptosis

Paclitaxel‐loaded polypeptide‐polyacrylamide nanomicelles overcome drug‐resistance by enhancing lysosomal membrane permeability and inducing apoptosis

Inhibition of Autophagy via Lysosomal Impairment Enhances Cytotoxicity of Fullerenol under Starvation Condition

Sequential Release of Paclitaxel and Imatinib from Core–Shell Microparticles Prepared by Coaxial Electrospray for Vaginal Therapy of Cervical Cancer

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