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1.
Pharmaceutics ; 15(2)2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36839675

RESUMO

Triple-negative breast cancer (TNBC) cells do not contain various receptors for targeted treatment, a reason behind the poor prognosis of this disease. In this study, biocompatible theranostic erythrocyte-derived nanoparticles (EDNs) were developed and evaluated for effective early diagnosis and treatment of TNBC. The anti-cancer drug, doxorubicin (DOX), was encapsulated into the EDNs and diagnostic quantum dots (QDs) were incorporated into the lipid bilayers of EDNs for tumor bio-imaging. Then, anti-epidermal growth factor receptor (EGFR) antibody molecules were conjugated to the surface of EDNs for TNBC targeting (iEDNs). According to the confocal microscopic analyses and biodistribution assay, iEDNs showed a higher accumulation in EGFR-positive MDA-MB-231 cancers in vitro as well as in vivo, compared to untargeted EDNs. iEDNs containing doxorubicin (iEDNs-DOX) showed a stronger inhibition of target tumor growth than untargeted ones. The resulting anti-EGFR iEDNs exhibited strong biocompatibility, prolonged blood circulation, and efficient targeting of TNBC in mice. Therefore, iEDNs may be used as potential TNBC-targeted co-delivery systems for therapeutics and diagnostics.

2.
Nanotechnol Sci Appl ; 15: 17-31, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35818431

RESUMO

Introduction: Avoiding phagocytic cells and reducing off-target toxicity are the primary hurdles in the clinical application of nanoparticles containing therapeutics. For overcoming these errors, in this study, nanoparticles expressing CD47 proteins inhibiting the phagocytic attack of immune cells were prepared and then evaluated as an anti-cancer drug delivery vehicle. Methods: The CD47+ cell-derived nanoparticles (CDNs) were prepared from the plasma membranes of human embryonic kidney cells transfected with a plasmid encoding CD47. And the doxorubicin (DOX) was loaded into the CDNs, and anti-EGF receptor (EGFR) antibodies were conjugated to the surface of the CDNs to target tumors overexpressing EGFR. Results: The CD47+iCDNs-DOX was successfully synthesized having a stable structure. The CD47+CDNs were taken up less by RAW264.7 macrophages compared to control CDNs. Anti-EGFR CD47+CDNs (iCDNs) selectively recognized EGFR-positive MDA-MB-231 cells in vitro and accumulated more effectively in the target tumor xenografts in mice. Moreover, iCDNs encapsulating doxorubicin (iCDNs-DOX) exhibited the highest suppression of tumor growth in mice, presumably due to the enhanced DOX delivery to tumor tissues, compared to non-targeting CDNs or CD47- iCDNs. Discussion: These results suggest that the clinical application of biocompatible cell membrane-derived nanocarriers could be facilitated by functionalization with macrophage-avoiding CD47 and tumor-targeting antibodies.

3.
Theranostics ; 9(3): 837-852, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30809312

RESUMO

Many aptamers have been evaluated for their ability as drug delivery vehicles to target ligands, and a variety of small interfering RNAs (siRNAs) have been tested for their anti-cancer properties. However, since these two types of molecules have similar physicochemical properties, it has so far been difficult to formulate siRNA-encapsulating carriers guided by aptamers. Here, we propose aptamer-coupled lipid nanocarriers encapsulating quantum dots (QDs) and siRNAs for theragnosis of triple-negative breast cancer (TNBC). Methods: Hydrophobic QDs were effectively incorporated into lipid bilayers, and then therapeutic siRNAs were complexed with QD-lipid nanocarriers (QLs). Finally, anti-EGFR aptamer-lipid conjugates were inserted into the QLs for TNBC targeting (aptamo-QLs). TNBC-targeting aptamo-QLs were directly compared to anti-EGFR antibody-coupled immuno-QLs. The in vitro delivery of therapeutic siRNAs and QDs to target cells was assessed by flow cytometry and confocal microscopy. The in vivo targeting of siRNAs to tumors and their therapeutic efficacy were evaluated in mice carrying MDA-MB-231 tumors. Results: Both types of EGFR-targeting QLs showed enhanced delivery to target cancer cells, resulting in more effective gene silencing and enhanced tumor imaging compared to non-targeting control QLs. Moreover, combinatorial therapy with Bcl-2 and PKC-ι siRNAs loaded into the anti-EGFR QLs was remarkably effective in inhibiting tumor growth and metastasis. Conclusion: In general, the aptamo-QLs showed competitive in vivo delivery and therapeutic efficacy compared to immuno-QLs under the same experimental conditions. Our results show that the anti-EGFR aptamer-guided lipid carriers may be a potential theranostic delivery vehicle for RNA interference and fluorescence imaging of TNBCs.


Assuntos
Antineoplásicos/administração & dosagem , Aptâmeros de Nucleotídeos/metabolismo , Receptores ErbB/metabolismo , Terapia de Alvo Molecular/métodos , RNA Interferente Pequeno/administração & dosagem , Nanomedicina Teranóstica/métodos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Animais , Linhagem Celular Tumoral , Portadores de Fármacos/administração & dosagem , Humanos , Lipossomos/administração & dosagem , Camundongos , Transplante de Neoplasias , Imagem Óptica/métodos , Pontos Quânticos/administração & dosagem , Transplante Heterólogo , Resultado do Tratamento , Neoplasias de Mama Triplo Negativas/diagnóstico
4.
Nanoscale ; 10(41): 19338-19350, 2018 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-30307008

RESUMO

Cancer theranosis is an emerging field of personalized medicine which enables individual anti-cancer treatment by monitoring the therapeutic responses of cancer patients. Based on a consideration of the nano-bio interactions related to the blood circulation of systemically administered nanoparticles in humans, as well as extravasation and active targeting, lipid micellar nanoparticles were co-loaded with paclitaxel (PTX) and quantum dots (QDs) to generate a theranostic delivery vehicle. To provide with a tumor-targeting capability, either an antibody or an aptamer against the epidermal growth factor receptor (EGFR) was conjugated to the micelle surface. The QD-containing micelles (QDMs), antibody-coupled QDMs (immuno-QDMs), and aptamer-coupled QDMs (aptamo-QDMs) were able to effectively circulate in blood for at least 8 h when administered intravenously into mice bearing EGFR-positive LS174T tumor xenografts. In vivo fluorescence imaging and a bio-distribution study showed that both the immuno-QDMs and aptamo-QDMs were largely localized in the tumor tissue. The tumor targeting capability enhanced the therapeutic efficacy of PTX for the target cancer cells. Both the immuno-PTX-QDMs and the aptamo-PTX-QDMs caused a stronger inhibition of LS174T tumor growth in mice, compared to the non-targeted PTX-QDMs. These results suggest that the anti-EGFR immuno-PTX-QDMs and anti-EGFR aptamo-PTX-QDMs could be utilized as a tumor-targeted theranostic delivery system for cancer treatment in the clinic.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Micelas , Neoplasias/tratamento farmacológico , Paclitaxel/administração & dosagem , Pontos Quânticos/química , Nanomedicina Teranóstica , Animais , Anticorpos Imobilizados/química , Anticorpos Imobilizados/imunologia , Antineoplásicos Fitogênicos/química , Aptâmeros de Nucleotídeos/química , Linhagem Celular Tumoral , Portadores de Fármacos/química , Portadores de Fármacos/metabolismo , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Receptores ErbB/química , Receptores ErbB/imunologia , Humanos , Camundongos , Nanopartículas/química , Neoplasias/diagnóstico por imagem , Neoplasias/patologia , Imagem Óptica , Paclitaxel/química , Distribuição Tecidual , Transplante Heterólogo
5.
Sci Rep ; 7(1): 9474, 2017 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-28842588

RESUMO

Co-application of fluorescent quantum dot nanocrystals and therapeutics has recently become a promising theranostic methodology for cancer treatment. We developed a tumor-targeted lipid nanocarrier that demonstrates notable efficacy in gene delivery as well as tumor bio-imaging. Coupling of aptamer molecules against the EGF receptor (EGFR) to the distal termini of lipid nanoparticles provided the carrier with tumor-specific recognition capability. The cationic lipid component, referred to as O,O'-dimyristyl-N-lysyl glutamate (DMKE), was able to effectively complex with anionic small-interfering RNA (siRNA). The hydrophobic quantum dots (Q-dots) were effectively incorporated in hydrophobic lipid bilayers at an appropriate Q-dot to lipid ratio. In this study, we optimized the liposomal formula of aptamer-conjugated liposomes containing Q-dots and siRNA molecules (Apt-QLs). The anti-EGFR Apt-QLs exhibited remarkable EGFR-dependent siRNA delivery as well as fluorescence imaging, which were analyzed in cultured cancer cells and tumor xenografts in mice. These results imply that the formulation of Apt-QLs could be widely utilized as a carrier for tumor-directed gene delivery and bio-imaging.


Assuntos
Aptâmeros de Nucleotídeos , Receptores ErbB/metabolismo , Técnicas de Transferência de Genes , Lipídeos/química , Imagem Molecular , Nanopartículas , Neoplasias/diagnóstico por imagem , Pontos Quânticos , Animais , Aptâmeros de Nucleotídeos/química , Linhagem Celular Tumoral , Modelos Animais de Doenças , Sistemas de Liberação de Medicamentos , Xenoenxertos , Humanos , Lipossomos , Camundongos , Microscopia de Fluorescência , Imagem Molecular/métodos , Nanopartículas/química , Neoplasias/metabolismo , Neoplasias/patologia
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