Olaparib@human serum albumin nanoparticles as sustained drug-releasing tumour-targeting nanomedicine to inhibit growth and metastasis in the mouse model of triple-negative breast cancer

Vysyaraju, Nageswara Rao; Paul, Milan; Ch, Sanjay; Ghosh, Balaram; Biswas, Swati

doi:10.1080/1061186x.2022.2092623

Cited by 8 publications

(17 citation statements)

References 54 publications

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“…After staining, they were washed with PBS, and the fluorescence was observed under the green channel of a fluorescence microscope. In the presence of ROS and cellular esterase, the acetate group is cleaved, and the molecule gets oxidized to form DCF, which produces fluorescence …”

Section: Methodsmentioning

confidence: 99%

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Dual-Drug-Loaded Topical Delivery of Photodynamically Active Lipid-Based Formulation for Combination Therapy of Cutaneous Melanoma

et al. 2023

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Topical administration of anti-cancer drugs along with photodynamically active molecules is a non-invasive approach, which stands to be a promising modality for treating aggressive cutaneous melanomas with the added advantage of high patient compliance. However, the efficiency of delivering drugs topically is limited by several factors, such as penetration of the drug across skin layers at the tumor site and limited light penetrability. In this study, curcumin, an active anti-cancer agent, and chlorin e6, a photoactivable molecule, were encapsulated into lipidic nanoparticles that produced reactive oxygen species (ROS) when activated at 665 nm by near-infrared (NIR) light. The optimized lipidic nanoparticle containing curcumin and chlorin e6 exhibited a particle size of less than 100 nm. The entrapment efficiency for both molecules was found to be 81%. The therapeutic efficacy of the developed formulation was tested on B16F10 and A431 cell lines via cytotoxicity evaluation, combination index, cellular uptake, nuclear staining, DNA fragmentation, ROS generation, apoptosis, and cell cycle assays under NIR irradiation (665 nm). Co-delivering curcumin and chlorin e6 exhibited higher cellular uptake, better cancer growth inhibition, and pronounced apoptotic events compared to the formulation having the free drug alone. The study results depicted that topical application of this ROS-generating dual-drug-loaded lipidic nanoparticles incorporated in SEPINEO gel achieved better permeation (80 ± 2.45%) across the skin, and exhibited the improved skin retention and a synergistic effect as well. The present work introduces photo-triggered ROS-generating dual-drug-based lipidic nanoparticles, which are simple and efficient to develop and exhibit synergistic therapeutic effects against cutaneous melanoma.

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Section: Methodsmentioning

confidence: 99%

“…In the presence of ROS and cellular esterase, the acetate group is cleaved, and the molecule gets oxidized to form DCF, which produces fluorescence. 33 2.6.7. Annexin-V Assay.…”

Section: Combination Index Analysismentioning

confidence: 99%

Dual-Drug-Loaded Topical Delivery of Photodynamically Active Lipid-Based Formulation for Combination Therapy of Cutaneous Melanoma

et al. 2023

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“…The KI-67 analysis was performed by the previously reported procedures. , In brief, tumor tissue sections were treated with a blocking buffer solution for 1 h and then stored overnight at 4 °C while being exposed to a primary antibody for KI-67. Following this, the sections were washed three times with PBS, and a secondary antibody (Alexa Fluor Plus 488) was applied for 2 h at 25 °C, with precautions being taken to avoid exposure to light.…”

Section: Methodsmentioning

confidence: 99%

“…The elevated decrease of tumor volume of DTX@ HOP NPs compared to that of free DTX could be attributed to the presence of HSA as the shell of the NPs, which increases its internalization to the tumor environment specifically, through GP60 and SPARC mechanism, thus increasing the site specificity which is not observed in the case of free drug treatment. 13,27,47 The mice were injected with D-luciferin and observed for the fluorescence intensity and tumor progression, as depicted in Figure 8E,G. The tumors extracted from all the mice of the different groups on day 21 were weighed and imaged, as represented in Figure 8D,F respectively.…”

Section: Tumor Inhibition Studymentioning

confidence: 99%

Synergistic Anticancer Response via Docetaxel- and Oleanolic Acid-Loaded Albumin/Poly(lactide) Nanoparticles in Triple-Negative Breast Cancer

Das,

Paul,

Ghosh

et al. 2023

ACS Appl. Nano Mater.

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Triple-negative breast cancer (TNBC) is the most aggressive form of breast cancer with a poor prognosis. A highly effective chemotherapeutic treatment strategy is yet to be developed that would kill cancer cells effectively and delay drug resistance. Combination therapy has emerged as a promising treatment strategy. Here, a human serum albumin/poly(d,l)-lactide core–shell nanoparticle system stabilized by a human serum albumin–oleanolic acid (HSA–OA) conjugate and loaded with docetaxel (DTX) and OA was developed. A thorough physicochemical characterization ensured efficient entrapment of DTX and OA. The synergistic inhibitory effect of DTX and OA via the developed nanoparticle (NP) system was investigated by using combination index analysis on human and murine TNBC, MDA-MB-231, and 4T1 cell lines. The uptake study, cell cycle analysis, apoptosis assay, DNA fragmentation study, reactive oxygen species generation, nuclear staining, and mitochondrial membrane potential assay indicated that the DTX/OA@HOP NPs provided the best inhibition and apoptotic effects when compared with free DTX, free OA, DTX@HOP NPs, and OA@HOP NPs. The in vivo study performed using 4T1-Luc tumor-bearing mice revealed that the DTX/OA@HOP NPs showed maximum tumor growth inhibition with a marked elevation in the apoptotic marker and decreased antiproliferative marker. Thus, the prepared DTX/OA@HOP NPs pose a promising combination therapy for the treatment of TNBC.

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“…The seeded cells were exposed to Ce6 and Ce6 formulations (Ce6 concentration of 10 μM) and PTX and PTX-H/P NPs (PTX concentration of 5 μM) for 24 h. The cells were laser-irradiated using a 660 nm laser at a power of 0.5 W/cm 2 after 12 h for 5 min and incubated for an additional 12 h. The assay was carried out by staining with PI and annexin V-FITC according to the protocol given in the TACS Annexin V assay kit and following the previously reported procedure. 23 The extent of apoptosis was evaluated by flow cytometry (FACS Aria III, BD Biosciences, and the USA).…”

Section: Cellular Uptake By Flow Cytometrymentioning

confidence: 99%

Concurrent Delivery of Paclitaxel and Chlorin e6 to Tumors Using Albumin/PLGA Nanoparticles for NIR Light-Triggered Chemo/Photodynamic Therapy

Paul

Bhatt

Kumbham

et al. 2023

ACS Appl. Nano Mater.

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In an attempt to develop a nanomedicine with the ability to produce combination chemo- and photodynamic therapeutic effects in cancer, herein, we fabricated poly(d,l-lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) using human serum albumin (HSA) as the surface modifier via the emulsification technique to co-deliver both a photosensitizer, chlorin e6 (Ce6), and a chemotherapeutic drug, paclitaxel (PTX). The Ce6/PTX-H/P NPs were characterized for size, morphology, drug loading, entrapment efficiencies, drug release, hemolytic tendency, and kinetic/storage stabilities by dynamic light scattering (DLS), scanning electron microscopy (SEM), ultraviolet (UV), infrared (IR), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and differential scanning calorimetry (DSC) analysis. The protein integrity in NPs was verified by circular dichroism (CD) spectroscopy and sodium dodecyl–sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The ability to generate reactive oxygen species (ROS) by Ce6 was monitored biochemically using DMA, RNO, and singlet oxygen sensor green (SOSG). Next, cell studies using murine melanoma (B16F10) and oral squamous cell carcinoma (FaDu) were performed to determine cellular uptake, laser irradiation-assisted cytotoxicity, combination drug effect, and cell death mechanisms. The in vivo therapeutic efficacy was analyzed using tumor (B16F10)-bearing mice. The NPs released both PTX and Ce6 sustainably with the enhancement of drug release at a low pH of 4.6. The Ce6/PTX-H/P NPs exhibited photostimulated ROS production, resulting in enhanced cytotoxicity than monotherapies and induced a synergistic therapeutic response in FaDu cells (24 and 48 h of treatment). The Ce6/PTX-H/P NPs exhibited extensive apoptotic induction, cell cycle arrest, DNA damage in the G2/M phase, and mitochondrial membrane perturbation compared to the free Ce6 and PTX and Ce6- or PTX-loaded NPs. The Ce6/PTX-H/P NPs reduced the tumor weight by 5.99% compared to the control and ∼2.66% compared to the free drugs, demonstrating the most effective treatment modality of all the tested formulations in the in vivo experiment using B16F10 tumor-bearing mice and in the immunohistochemistry analysis. Ce6/PTX-H/P NPs could be a promising treatment option for solid tumors.

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Olaparib@human serum albumin nanoparticles as sustained drug-releasing tumour-targeting nanomedicine to inhibit growth and metastasis in the mouse model of triple-negative breast cancer

Cited by 8 publications

References 54 publications

Dual-Drug-Loaded Topical Delivery of Photodynamically Active Lipid-Based Formulation for Combination Therapy of Cutaneous Melanoma

Dual-Drug-Loaded Topical Delivery of Photodynamically Active Lipid-Based Formulation for Combination Therapy of Cutaneous Melanoma

Synergistic Anticancer Response via Docetaxel- and Oleanolic Acid-Loaded Albumin/Poly(lactide) Nanoparticles in Triple-Negative Breast Cancer

Concurrent Delivery of Paclitaxel and Chlorin e6 to Tumors Using Albumin/PLGA Nanoparticles for NIR Light-Triggered Chemo/Photodynamic Therapy

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