How to Train Your Dragon: Targeted Delivery of MicroRNA to Cancer Cells In Vivo

The targeted delivery of nanomedicines into solid tumors remains challenging in cancer treatment. Stem cells with tumortropic migration ability are promising as biocarriers to transport nanomedicines. The transportation of nanomedicines into cancer cells is the key step for tumor targeted delivery via stem cells. In this study, we designed a magnetic nanocube (scMNP) loaded in mesenchymal stem cells for magnetic hyperthermia of prostate cancer, and the delivery and transportation pathways into the cancer cells were fully investigated. The MSCs acted as the carrier of the loaded scMNPs along with the upregulation of CXCR4 for the migration to cancer cells. The therapeutic effect was mainly due to scMNPs via magnetic hyperthermia. Stem cell-derived microvesicles containing scMNPs played an essential role in the crosstalk between stem cells and cancer cells for targeted delivery. Both in vitro and in vivo studies demonstrated that the system showed satisfactory therapeutic efficiency under magnetic hyperthermia therapy. Our investigation presents a comprehensive study of magnetic nanoparticles in combination with MSCs and their extracellular microvesicles and is promising as an effective strategy for magnetic hyperthermia therapy of prostate cancer.

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Transferrin-Conjugated Polymeric Nanoparticle for Receptor-Mediated Delivery of Doxorubicin in Doxorubicin-Resistant Breast Cancer Cells

Pharmaceutics ◽

10.3390/pharmaceutics11020063 ◽

2019 ◽

Vol 11 (2) ◽

pp. 63 ◽

Cited By ~ 15

Author(s):

Zar Chi Soe ◽

Jun Bum Kwon ◽

Raj Kumar Thapa ◽

Wenquan Ou ◽

Hanh Thuy Nguyen ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Cell Lines ◽

Targeted Delivery ◽

Poloxamer 407 ◽

Multi Drug Resistance ◽

Breast Cancer Cell Lines ◽

Polymeric Nanoparticle ◽

Cellular Apoptosis

In this study, a transferrin (Tf)-conjugated polymeric nanoparticle was developed for the targeted delivery of the chemotherapeutic agent doxorubicin (Dox) in order to overcome multi-drug resistance in cancer treatment. Our objective was to improve Dox delivery for producing significant antitumor efficacy in Dox-resistant (R) breast cancer cell lines with minimum toxicity to healthy cells. The results of our experiments revealed that Dox was successfully loaded inside a transferrin (Tf)-conjugated polymeric nanoparticle composed of poloxamer 407 (F127) and 123 (P123) (Dox/F127&P123-Tf), which produced nanosized particles (~90 nm) with a low polydispersity index (~0.23). The accelerated and controlled release profiles of Dox from the nanoparticles were characterized in acidic and physiological pH and Dox/F127&P123-Tf enhanced Dox cytotoxicity in OVCAR-3, MDA-MB-231, and MDA-MB-231(R) cell lines through induction of cellular apoptosis. Moreover, Dox/F127&P123-Tf inhibited cell migration and altered the cell cycle patterns of different cancer cells. In vivo study in MDA-MB-231(R) tumor-bearing mice demonstrated enhanced delivery of nanoparticles to the tumor site when coated in a targeting moiety. Therefore, Dox/F127&P123-Tf has been tailored, using the principles of nanotherapeutics, to overcome drug-resistant chemotherapy.

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Targeting Cancer Resistance via Multifunctional Gold Nanoparticles

International Journal of Molecular Sciences ◽

10.3390/ijms20215510 ◽

2019 ◽

Vol 20 (21) ◽

pp. 5510 ◽

Cited By ~ 3

Author(s):

Pedro Pedrosa ◽

M. Luísa Corvo ◽

Margarida Ferreira-Silva ◽

Pedro Martins ◽

Manuela Colla Carvalheiro ◽

...

Keyword(s):

Gold Nanoparticles ◽

Cancer Cells ◽

Targeted Delivery ◽

Drug Stability ◽

Chemotherapeutic Agents ◽

In Vivo Studies ◽

Cancer Resistance ◽

Selective Targeting ◽

New Compounds

Resistance to chemotherapy is a major problem facing current cancer therapy, which is continuously aiming at the development of new compounds that are capable of tackling tumors that developed resistance toward common chemotherapeutic agents, such as doxorubicin (DOX). Alongside the development of new generations of compounds, nanotechnology-based delivery strategies can significantly improve the in vivo drug stability and target specificity for overcoming drug resistance. In this study, multifunctional gold nanoparticles (AuNP) have been used as a nanoplatform for the targeted delivery of an original anticancer agent, a Zn(II) coordination compound [Zn(DION)2]Cl2 (ZnD), toward better efficacy against DOX-resistant colorectal carcinoma cells (HCT116 DR). Selective delivery of the ZnD nanosystem to cancer cells was achieved by active targeting via cetuximab, NanoZnD, which significantly inhibited cell proliferation and triggered the death of resistant tumor cells, thus improving efficacy. In vivo studies in a colorectal DOX-resistant model corroborated the capability of NanoZnD for the selective targeting of cancer cells, leading to a reduction of tumor growth without systemic toxicity. This approach highlights the potential of gold nanoformulations for the targeting of drug-resistant cancer cells.

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A novel aptamer-based DNA diamond nanostructure for in vivo targeted delivery of epirubicin to cancer cells

RSC Advances ◽

10.1039/c6ra28234b ◽

2017 ◽

Vol 7 (25) ◽

pp. 15181-15188 ◽

Cited By ~ 11

Author(s):

Khalil Abnous ◽

Noor Mohammad Danesh ◽

Mohammad Ramezani ◽

Parirokh Lavaee ◽

Seyed Hamid Jalalian ◽

...

Keyword(s):

Cancer Cells ◽

Targeted Delivery

The clinical administration of epirubicin (Epi) in the treatment of cancer has been restricted, owing to its cardiotoxicity.

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Dual peptide-mediated targeted delivery of bioactive siRNAs to oral cancer cells in vivo

Oral Oncology ◽

10.1016/j.oraloncology.2017.07.004 ◽

2017 ◽

Vol 72 ◽

pp. 123-131 ◽

Cited By ~ 8

Author(s):

Angela A. Alexander-Bryant ◽

Haiwen Zhang ◽

Christopher C. Attaway ◽

William Pugh ◽

Laurence Eggart ◽

...

Keyword(s):

Oral Cancer ◽

Cancer Cells ◽

Targeted Delivery ◽

Oral Cancer Cells

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Smart aptamer-modified calcium carbonate nanoparticles for controlled release and targeted delivery of epirubicin and melittin into cancer cells in vitro and in vivo

Drug Development and Industrial Pharmacy ◽

10.1080/03639045.2019.1569029 ◽

2019 ◽

Vol 45 (4) ◽

pp. 603-610 ◽

Cited By ~ 10

Author(s):

Rezvan Yazdian-Robati ◽

Atefeh Arab ◽

Mohammad Ramezani ◽

Houshang Rafatpanah ◽

Amirhossein Bahreyni ◽

...

Keyword(s):

Calcium Carbonate ◽

Controlled Release ◽

Cancer Cells ◽

Targeted Delivery

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Polyethylene Glycol Conjugated Polymeric Nanocapsules for Targeted Delivery of Quercetin to Folate-Expressing Cancer Cells in Vitro and in Vivo

ACS Nano ◽

10.1021/nn405155b ◽

2014 ◽

Vol 8 (2) ◽

pp. 1384-1401 ◽

Cited By ~ 95

Author(s):

Riham I. El-Gogary ◽

Noelia Rubio ◽

Julie Tzu-Wen Wang ◽

Wafa’ T. Al-Jamal ◽

Maxime Bourgognon ◽

...

Keyword(s):

Polyethylene Glycol ◽

Cancer Cells ◽

Targeted Delivery ◽

Polymeric Nanocapsules

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Overcoming Drug Resistance in Colon Cancer by Aptamer-Mediated Targeted Co-Delivery of Drug and siRNA Using Grapefruit-Derived Nanovectors

Cellular Physiology and Biochemistry ◽

10.1159/000493960 ◽

2018 ◽

Vol 50 (1) ◽

pp. 79-91 ◽

Cited By ~ 7

Author(s):

Wei Yan ◽

Mingyue Tao ◽

Baofei Jiang ◽

Mengchu Yao ◽

Yali Jun ◽

...

Keyword(s):

Colon Cancer ◽

Cancer Cells ◽

Targeted Delivery ◽

Glycoprotein P ◽

Anti Cancer ◽

Lovo Cells ◽

Si Rna ◽

Cancer Activity

Background/Aims: Multidrug resistance (MDR) is the most common cause of chemotherapy failure. Upregulation of P-glycoprotein (P-gp) is one of the main mechanisms underlying MDR. Methods: In this study, we developed a targeted drug and small interfering (si)RNA co-delivery system based on specific aptamer-conjugated grapefruit-derived nanovectors (GNVs) that we tested in MDR LoVo colon cancer cells. The internalization of nanovectors in cancer cells was tested by fluorescence microscopy and flow cytometry. The anti-cancer activity in vitro was determined by colony formation and cell apoptosis assays. The biodistribution of nanovectors was analyzed by live imaging and the anti-cancer activity in vivo was observed. Results: GNVs loaded with aptamer increased doxorubicin (Dox) accumulation in MDR LoVo cells, an effect that was abolished by pretreatment with DNase. The LA1 aptamer effectively promoted nanovector internalization into cells at 4°C and increased the targeted delivery of Dox to tumors. Constructs harboring Dox, LA1, and P-gp siRNA more effectively inhibited proliferation and enhanced apoptosis in cultured MDR LoVo cells while exhibiting more potent anti-tumor activity in vivo than free Dox or GNVs loaded with Dox alone or in conjunction with LA1, an effect that was associated with downregulation of P-gp expression. Conclusion: This GNV-based system may be an effective strategy for overcoming MDR in clinical settings.

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Cancer cell-targeted cisplatin prodrug delivery in vivo via metabolic labeling and bioorthogonal click reaction

Biomaterials Science ◽

10.1039/d0bm01709d ◽

2021 ◽

Author(s):

Xun Liu ◽

Fan Wu ◽

Kaimin Cai ◽

Ziyin Zhao ◽

Zhimin Zhang ◽

...

Keyword(s):

Click Chemistry ◽

Cancer Cells ◽

Cancer Cell ◽

Targeted Delivery ◽

Click Reaction ◽

Metabolic Labeling

DCL-AAM selectively labels cancer cells with azido groups, and thus allows tumor-targeted delivery of DBCO-cisplatin prodrug via bioorthogonal click chemistry.

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Lipidated Peptidomimetic Ligand-Functionalized HER2 Targeted Liposome as Nano-Carrier Designed for Doxorubicin Delivery in Cancer Therapy

Pharmaceuticals ◽

10.3390/ph14030221 ◽

2021 ◽

Vol 14 (3) ◽

pp. 221

Author(s):

Himgauri Naik ◽

Jafrin Jobayer Sonju ◽

Sitanshu Singh ◽

Ioulia Chatzistamou ◽

Leeza Shrestha ◽

...

Keyword(s):

Cell Viability ◽

Cancer Cells ◽

Cellular Uptake ◽

Targeted Delivery ◽

Chemotherapeutic Agents ◽

In Vivo Studies ◽

Breast Cancer Cell Lines ◽

In Vivo Evaluation ◽

Lipid Film

The therapeutic index of chemotherapeutic agents can be improved by the use of nano-carrier-mediated chemotherapeutic delivery. Ligand-targeted drug delivery can be used to achieve selective and specific delivery of chemotherapeutic agents to cancer cells. In this study, we prepared a peptidomimetic conjugate (SA-5)-tagged doxorubicin (Dox) incorporated liposome (LP) formulation (SA-5-Dox-LP) to evaluate the targeted delivery potential of SA-5 in human epidermal growth factor receptor-2 (HER2) overexpressed non-small-cell lung cancer (NSCLC) and breast cancer cell lines. The liposome was prepared using thin lipid film hydration and was characterized for particle size, encapsulation efficiency, cell viability, and targeted cellular uptake. In vivo evaluation of the liposomal formulation was performed in a mice model of NSCLC. The cell viability studies revealed that targeted SA-5-Dox-LP showed better antiproliferative activity than non-targeted Dox liposomes (Dox-LP). HER2-targeted liposome delivery showed selective cellular uptake compared to non-targeted liposomes on cancer cells. In vitro drug release studies indicated that Dox was released slowly from the formulations over 24 h, and there was no difference in Dox release between Dox-LP formulation and SA-5-Dox-LP formulation. In vivo studies in an NSCLC model of mice indicated that SA-5-Dox-LP could reduce the lung tumors significantly compared to vehicle control and Dox. In conclusion, this study demonstrated that the SA-5-Dox-LP liposome has the potential to increase therapeutic efficiency and targeted delivery of Dox in HER2 overexpressing cancer.

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