Emergence of Nanotechnology as a Powerful Cavalry against Triple-Negative Breast Cancer (TNBC)

Chaudhuri, Aiswarya; Kumar, Dulla Naveen; Deepa, D; Singh, Sanjay; Kumar, Pradeep; Bolla, Pradeep Kumar; Kumar, Dinesh; Agrawal, Ashish Kumar

doi:10.3390/ph15050542

Cited by 21 publications

(17 citation statements)

References 314 publications

(355 reference statements)

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“…Radiation therapy, surgery, and chemotherapy are the therapy options available for breast cancer treatment. Among the stated therapeutic options, systemic chemotherapy is considered an attainable, potent, and cornerstone therapeutic strategy for the treatment of breast cancer [ 2 , 3 ].…”

Section: Introductionmentioning

confidence: 99%

Combination Therapy Comprising Paclitaxel and 5-Fluorouracil by Using Folic Acid Functionalized Bovine Milk Exosomes Improves the Therapeutic Efficacy against Breast Cancer

Kumar

Chaudhuri

Deepa

et al. 2022

Life

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Paclitaxel (PAC) has been approved by FDA for clinical use (Taxol®), yet dose-dependent severe toxicity due to the adjuvant Cremophor EL® in combination with ethanol is a major drawback. The drawbacks of the current therapy can be overcome by (i) finding a suitable vehicle that cannot only bypass the above adjuvant but also be used to deliver drugs orally and (ii) combining the PAC with some other chemotherapeutics to have the enhanced therapeutic efficacy. In the current work, we have used folic acid (FA) functionalized bovine milk-derived exosomes for oral delivery of PAC in combination with 5-fluorouracil (5-FU). Exosomes before and after the drug loading were found to have a particle size in the range of 80–100 nm, polydispersity index (PDI ~0.20), zeta potential (~−25 mV), entrapment efficiency (~82%), practical drug loading (~28%) and sustained drug release for 48 h. Significant decreases in IC50 were observed in the case of exosomes loaded drugs which further improved following the FA functionalization. FA functionalized coumarin-6-loaded exosomes showed remarkably higher cellular uptake in comparison with free coumarin-6. Moreover, FA-functionalized drug-loaded exosomes showed a higher apoptotic index with better control over cell migration. Collectively, data suggested the enhanced efficacy of the combination following its loading to the folic acid functionalized exosomes against breast cancer.

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Section: Introductionmentioning

confidence: 99%

Combination Therapy Comprising Paclitaxel and 5-Fluorouracil by Using Folic Acid Functionalized Bovine Milk Exosomes Improves the Therapeutic Efficacy against Breast Cancer

Kumar

Chaudhuri

Deepa

et al. 2022

Life

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“…In recent years, nanoparticle drug delivery systems are emerging as promising approaches to enhance the therapeutic e cacy for the chemotherapy of TNBC [14,15]. Over the past decades, exosomes have been increasingly considered as biological substitutes for nanoparticle drug delivery systems.…”

Section: Introductionmentioning

confidence: 99%

Paclitaxel-loaded hybrid exosome for targeted chemotherapy of triple-negative breast cancer

Liu

Tang

et al. 2022

Preprint

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Background: Triple-negative breast cancer (TNBC) is a highly invasive malignant tumor with bleak prognosis.Paclitaxel (PTX) is the first-line chemotherapeutic drug for TNBC management. It is of great significance to develop carriers for targeted delivery of PTX to enhance the anti-tumor efficacy and reduce the side effects for TNBC management. Exosomes are small extracellular vesicles and emerging competent nanocarriers for targeted drug delivery. However, the application of exosomes has been challenged by the production, drug loading and quality control. The introduction of synthetic nanomaterials may help to overcome the limitations of exosomes and generate alternatives. Herein, we performed a biohybrid approach to fuse exosomeswith liposomes to produce hybrid exosome (HE) with improved PTX loading capacity and enhanced tumor-targeting ability for TNBC chemotherapy. Methods:HE and PTX-loaded HE (PTX-HE) were prepared by co-extrusion of exosomes with liposome (lipo) or PTX-loaded liposome (PTX-lipo) respectively. The size distribution of HE was measured by nanoparticle tracking analysis (NTA) and dynamic laser-light scattering (DLS). The morphology was observed by transmission electron microscopy (TEM). The protein profile of HE was determined by western blot and Coomassie Blue staining. Drug loading capacity and encapsulation efficiency were measured by high-performance liquid chromatography (HPLC). Cellular uptake, tumor cell killing effect and anti-migration ability of PTX-HE were evaluated in vitro. Biodistribution, anti-tumor therapeutic efficacy and safety of PTX-HE were evaluated in orthotopic TNBC mice models. Results:The characterization results manifested HE was spherical structure with uniform size distribution (157.28 nm). HE had improved loading capacity (6.20 ± 0.79%) and higher encapsulation efficiency (86.79 ± 11.07%) of PTX than lipo. More importantly, PTX-HE possessed higher cellular uptake efficiency, lower IC50 (4.32 ± 0.48 μg/mL) and stronger anti-migration ability (cell mobility: 16%) as compared with PTX-lipo. In TNBC-bearing mice, PTX-HE accumulated at tumor sites and suppressed tumor growth (tumor inhibition rate: 60%) with minimal systemic toxicity. Conclusions: HE exhibits improved drug loading capacity, targeting ability and cancer cell-killing effect. Overall, HE developed by fusing exosomes with liposomes provides a promising strategy for the large-scale generation of exosome alternatives as drug carriers for targeted chemotherapy.

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“…Breast cancer ranks the first in the incidence and mortality of malignant tumors in Chinese women, and the incidence is still rising [ 1 , 2 ]. Breast cancer has undoubtedly become a major threat to women’s health globally.…”

Section: Introductionmentioning

confidence: 99%

Tiliroside suppresses triple-negative breast cancer as a multifunctional CAXII inhibitor

Han

Yang

Lü³

et al. 2022

Cancer Cell Int

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Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer characterized by poor prognosis, early recurrence, and the lack of durable chemotherapy responses and specific targeted treatments. In this preclinical study, we examines Tiliroside (TS, C30H26O13), as one of the major compounds of Tribulus terrestris L. which has been used as an alternative therapy in clinic practice of breast cancer treatment, for its therapeutic use in TNBC. The association between CAXII expression level and survival probability of TNBC patients, and the difference of CAXII expression level between TNBC and normal samples were evaluated by using publicly accessible databases. To determine the anticancer efficacy of TS on TNBC cells, cell proliferation, wound healing, cell invasion, and 3D spheroid formation assays were performed and excellent anticancer activities of TS were displayed. Mouse models further demonstrated that TS significantly reduced the tumor burden and improved survival rate. The properties of TS as a novel CAXII inhibitor have also been evaluated by CAXII activity assay, pHi, pHe and lactate level assay. Further RT-PCR and Caspase-3 activity analyses also revealed the positive regulating effects of TS on E2F1,3/Caspase-3 axis in TNBC cells cultured in 2D or 3D systems. The findings indicate that TS suppresses TNBC progression as a potential novel CAXII inhibitor in preclinical experiments, which warrants further investigation on its therapeutic implications.

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Emergence of Nanotechnology as a Powerful Cavalry against Triple-Negative Breast Cancer (TNBC)

Cited by 21 publications

References 314 publications

Combination Therapy Comprising Paclitaxel and 5-Fluorouracil by Using Folic Acid Functionalized Bovine Milk Exosomes Improves the Therapeutic Efficacy against Breast Cancer

Combination Therapy Comprising Paclitaxel and 5-Fluorouracil by Using Folic Acid Functionalized Bovine Milk Exosomes Improves the Therapeutic Efficacy against Breast Cancer

Paclitaxel-loaded hybrid exosome for targeted chemotherapy of triple-negative breast cancer

Tiliroside suppresses triple-negative breast cancer as a multifunctional CAXII inhibitor

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