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1.
Adv Healthc Mater ; 13(7): e2302549, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38059737

RESUMO

In this work, we proposed nµPEF, a novel pulse configuration combining nanosecond and microsecond pulses (nµPEF), to enhance tumor ablation in irreversible electroporation (IRE) for oncological therapy. nµPEF demonstrated improved efficacy in inducing immunogenic cell death, positioning it as a potential candidate for next-generation ablative therapy. However, the immune response elicited by nµPEF alone was insufficient to effectively suppress distant tumors. To address this limitation, we developed PPR@CM-PD1, a genetically engineered nanovesicle. PPR@CM-PD1 employed a polyethylene glycol-polylactic acid-glycolic acid (PEG-PLGA) nanoparticle encapsulating the immune adjuvant imiquimod and coated with a genetically engineered cell membrane expressing programmed cell death protein 1 (PD1). This design allowed PPR@CM-PD1 to target both the innate immune system through toll-like receptor 7 (TLR7) agonism and the adaptive immune system through programmed cell death protein 1/programmed cell death-ligand 1 (PD1/PDL1) checkpoint blockade. In turn, nµPEF facilitated intratumoral infiltration of PPR@CM-PD1 by modulating the tumor stroma. The combination of nµPEF and PPR@CM-PD1 generated a potent and systemic antitumor immune response, resulting in remarkable suppression of both nµPEF-treated and untreated distant tumors (abscopal effects). This interdisciplinary approach presents a promising perspective for oncotherapy and holds great potential for future clinical applications.


Assuntos
Neoplasias , Receptor de Morte Celular Programada 1 , Humanos , Imunoterapia/métodos , Imunidade , Adjuvantes Imunológicos , Eletroporação/métodos
2.
Discov Oncol ; 14(1): 164, 2023 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-37665421

RESUMO

INTRODUCTION: Natural killer cells can attack cancer cells without prior sensitization, but their clinical benefit is limited owing to their poor selectivity that is caused by the lack of specific receptors to target tumor cells. In this study, we aimed to endow NK cells with the ability to specifically target glypican-3+ tumor cells without producing cell damage or genetic alterations, and further evaluated their therapeutic efficiency. METHODS: NK cells were modified with a Gpc3 DNA aptamer on the cell surface via metabolic glycoengineering to endow NK cells with specific targeting ability. Then, the G-NK cells were evaluated for their specific targeting properties, cytotoxicity and secretion of cytokines in vitro. Finally, we investigated the therapeutic efficiency of G-NK cells against glypican-3+ tumor cells in vivo. RESULTS: Compared with NK cells modified with a random aptamer mutation and unmodified NK cells, G-NK cells induced significant apoptosis/necrosis of GPC3+ tumor cells and secreted cytokines to preserve the intense cytotoxic activities. Moreover, G-NK cells significantly suppressed tumor growth in HepG2 tumor-bearing mice due to the enhanced enrichment of G-NK cells at the tumor site. CONCLUSIONS: The proposed strategy endows NK cells with a tumor-specific targeting ability to enhance adoptive therapeutic efficiency in GPC3+ hepatocellular carcinoma.

3.
Pharmaceutics ; 14(5)2022 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-35631661

RESUMO

Phototherapy, including photothermal therapy (PTT) and photodynamic therapy (PDT) has attracted growing attention as a noninvasive option for cancer treatment. At present, researchers have developed various "all-in-one" nanoplatforms for cancer imaging and PTT/PDT combinational therapy. However, the complex structure, tedious preparation procedures, overuse of extra carriers and severe side effects hinder their biomedical applications. In this work, we reported a nanoplatform (designated as ICG-MB) self-assembly from two different FDA-approved dyes of indocyanine green (ICG) and methylene blue (MB) without any additional excipients for cancer fluorescence imaging and combinational PTT/PDT. ICG-MB was found to exhibit good dispersion in the aqueous phase and improve the photostability and cellular uptake of free ICG and MB, thus exhibiting enhanced photothermal conversion and singlet oxygen (1O2) generation abilities to robustly ablate cancer cells under 808 nm and 670 nm laser irradiation. After intravenous injection, ICG-MB effectively accumulated at tumor sites with a near-infrared (NIR) fluorescence signal, which helped to delineate the targeted area for NIR laser-triggered phototoxicity. As a consequence, ICG-MB displayed a combinational PTT/PDT effect to potently inhibit tumor growth without causing any system toxicities in vivo. In conclusion, this minimalist, effective and biocompatible nanotheranostic would provide a promising candidate for cancer phototherapy based on current available dyes in clinic.

4.
J Mater Chem B ; 9(25): 5083-5091, 2021 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-34124729

RESUMO

Photothermal therapy (PTT) exhibits an excellent therapeutic effect in cancer treatment, but some cancers are still facing rapid recurrence due to the presence of heat-resistant cells, which express heat shock proteins (HSP) to defend against hyperthermia. Inspired by optogenetics, we firstly designed a caged TNF-related apoptosis-inducing ligand (TRAIL) expressing plasmid under HSP70 protomer (HSP70-TRAIL) as the thermal-activated gene therapy agent to induce the apoptosis of heat resistant cells. Then, the caged HSP70-TRAIL was decorated on the surface of the photothermal agent (semiconducting nanoparticles, SPNs) through electrostatic adsorption to obtain SPN@HSP70-TRAIL-GFP (SPNHT). Under 1064 nm near-infrared second region (NIR-II) laser irradiation, the SPNHT acted as an emerging photothermal agent for PTT. Importantly, the caged HSP70-TRAIL could be further activated by PTT to express TRAIL on demand to concurrently kill survival cells for overcoming the problem of tumor recurrence after PTT. Both in vitro and in vivo studies demonstrated that the SPNHT nano-system with the ability of NIR-II photothermal-triggered TRAIL in situ expression possessed an admirable synergistic anti-cancer efficacy for HCC. This work offers new tactics for effective treatment of cancer, which showed a great significance for reducing the rate of cancer recurrence after PTT treatment.


Assuntos
Antineoplásicos/farmacologia , Materiais Biocompatíveis/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Fármacos Fotossensibilizantes/farmacologia , Terapia Fototérmica , Adsorção , Animais , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Materiais Biocompatíveis/química , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Neoplasias Hepáticas Experimentais/patologia , Camundongos , Imagem Óptica , Fármacos Fotossensibilizantes/química
5.
Int J Nanomedicine ; 16: 2879-2896, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33883896

RESUMO

BACKGROUND: Effective treatment strategy for cervical carcinoma is subject to the limitation of its anatomical location and histological characteristics. Comprehensive imaging before cervical carcinoma treatment is of great significance for the patients. Current imaging methods cannot meet the requirements of high resolution, deep imaging depth and non-invasive imaging at the same time. Fortunately, Photoacoustic imaging (PAI) is a novel imaging method that combines rich optical contrast, high ultrasonic spatial resolution, and deep penetration depth in a single modality. Moreover, PAI-guided photothermal therapy (PTT) by aid of targeting nanoparticles is an emerging and effective cancer treatment in recent years. METHODS: Here, strong near-infrared region (NIR) absorption-conjugated polymer PIIGDTS (PD) nanoparticles with folic acid (FA) modification (namely, PD-FA) that targeted at Hela cell were specifically designed as cervical tumor imaging contrast agents and photothermal agents. RESULTS: The obtained PD-FA nanoparticles exhibited admirable photoacoustic contrast-enhancing ability and desirable PTT behavior with the photothermal conversion efficiency as high as 62.6% in vitro. Furthermore, the PAI performance and PTT efficiency were tested in HeLa tumor-bearing nude mice after injection of PD-FA nanoparticles. In vivo multi-scale, PAI provided B-san and 3D dimension imaging for intuitive and comprehensive information of Hela tumor. Moreover, the Hela tumor can be completely eliminated within 18 days after PTT, with no toxicity and side effects. CONCLUSION: In summary, PD-FA injection combined with PAI and PTT systems provides a novel powerful tool for early diagnosis and precise treatment of cervical cancer.


Assuntos
Lasers , Nanopartículas/química , Técnicas Fotoacústicas/métodos , Terapia Fototérmica , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/terapia , Animais , Células COS , Chlorocebus aethiops , Feminino , Ácido Fólico/química , Células HeLa , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/administração & dosagem , Nanopartículas/ultraestrutura , Especificidade de Órgãos , Imagens de Fantasmas , Polímeros/química
6.
Adv Healthc Mater ; 10(10): e2002036, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33644987

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common and deadliest malignancy cancers, which remains a major global health problem. At present, over 50% of patients with HCC have implemented systemic therapies, such as interventional therapy or local chemotherapy that are scarcely effective and induce serious side effects to the remaining normal liver, further limiting their clinical outcomes. Herein, a tumor microenvironment triggered cascade-activation nanoplatform (A-NPLap/TPZ ) is prepared based on ß-lapachone (ß-Lap) and tirapazamine (TPZ) for the synergistic therapy of HCC. The A-NPLap/TPZ exerts its targeting effect by binding to the receptor of tumor cells with an external aptamer. In the tumor microenvironment, the nanoplatform can realize H2 O2 -triggered disassembly to release ß-Lap and TPZ. The released ß-Lap generates ROS to induce tumor cell apoptosis under the catalysis of the tumor cell over-expressed NAD(P)H-quinone oxidoreductase-1 (NQO1) enzyme. In this process, oxygen is consumed to intensify tumor hypoxia, and eventually cascade activates TPZ to exert the anti-tumor effect. The studies in vitro and in vivo consistently demonstrate that the as-prepared A-NPLap/TPZ nanoplatform possesses an excellent synergistic anti-tumor effect. This design of nanoplatform with cascade activation effect provides a promising strategy for HCC treatment.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/tratamento farmacológico , Linhagem Celular Tumoral , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Tirapazamina , Hipóxia Tumoral , Microambiente Tumoral
7.
Nanoscale ; 12(38): 19665-19672, 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-32966502

RESUMO

Photothermal therapy (PTT), a powerful tool for non-invasive cancer treatment, has been recognized as an alternative strategy for cancer therapy in the clinic, and it is promoted by optical absorbing agents (photothermal agents) that can intensively convert near-infrared (NIR) light into thermal energy for cancer ablation. Conjugated polymer nanoparticles (CPNs) have recently attracted extensive attention owing to their excellent photothermal properties. However, the absorption of typical CPNs is mostly located in the traditional near-infrared region (NIR-I, 700-900 nm), which suffers from low tissue penetration, so the penetration depth is still limited and severely restricts their further applications. Compared with the NIR-I light, the second near-infrared window light (NIR-II, 1000-1700 nm) could efficiently enhance the tissue penetration depth, however, CPNs which absorb NIR-II region light are still especially limited and need further exploration. Here, a thieno-isoindigo derivative-based Donor-Acceptor (D-A) polymer (BTPBFDTS), which exhibited excellent absorption characteristics from the NIR-I to NIR-II window, was prepared. After formation of nanoparticles and surface functionalization, the prepared nanoparticles (NPsBTPBFDTS@HA NPs) exhibited obvious targeting ability, high photothermal conversion efficiency and photoacoustic imaging effects under 1064 nm irradiation. Both in vitro and in vivo studies demonstrate that our obtained NPsBTPBFDTS@HA nanoparticles possess excellent PTT efficacy including extremely high cancer cell killing ability and admirable tumor elimination efficiency. Hence, this work developed a promising photothermal conversion agent based on CPNs for cancer ablation.


Assuntos
Nanopartículas , Neoplasias , Humanos , Raios Infravermelhos , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Fototerapia , Terapia Fototérmica , Polímeros
8.
iScience ; 23(7): 101341, 2020 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-32683314

RESUMO

Immune cold tumor characterized by low immunogenicity, insufficient and exhausted tumor-infiltrating lymphocytes, and immunosuppressive microenvironment is the main bottleneck responsible for low patient response rate of immune checkpoint blockade. Here, we developed biosynthetic functional vesicles (BFVs) to convert immune cold into hot through overcoming hypoxia, inducing immunogenic cell death, and immune checkpoint inhibition. The BFVs present PD1 and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) on the surface, whereas load catalase into their inner core. The TRAIL can specifically induce immunogenic death of cancer cells to initiate immune response, which is further synergistically strengthened by blocking PD1/PDL1 checkpoint signal through ectogenic PD1 proteins on BFVs. The catalase can produce O2 to overcome tumor hypoxia, in turn to increase infiltration of effector T cells while deplete immunosuppressive cells in tumor. The BFVs elicit robust and systematic antitumor immunity, as demonstrated by significant regression of tumor growth, prevention of abscopal tumors, and excellent inhibition of lung metastasis.

9.
Chem Commun (Camb) ; 56(7): 1093-1096, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31894764

RESUMO

We prepared novel conjugated polymer based NIR-II nanoparticles, which display extremely high photothermal conversion efficiency (65%). Both in vitro and in vivo investigations revealed that the as-prepared nanoparticles exhibit excellent theranostic properties including an extremely high cancer cell killing ability, admirable tumor elimination efficiency (100%) and a remarkable photoacoustic imaging contrast enhancing ability.


Assuntos
Antineoplásicos/uso terapêutico , Nanopartículas/uso terapêutico , Compostos de Organossilício/uso terapêutico , Polímeros/uso terapêutico , Tiadiazóis/uso terapêutico , Animais , Antineoplásicos/química , Antineoplásicos/efeitos da radiação , Células Hep G2 , Humanos , Hipertermia Induzida/métodos , Raios Infravermelhos , Camundongos , Microscopia Confocal/métodos , Microscopia de Fluorescência/métodos , Nanopartículas/química , Nanopartículas/efeitos da radiação , Compostos de Organossilício/química , Compostos de Organossilício/efeitos da radiação , Técnicas Fotoacústicas/métodos , Polímeros/química , Polímeros/efeitos da radiação , Nanomedicina Teranóstica/métodos , Tiadiazóis/química , Tiadiazóis/efeitos da radiação
10.
Nanomicro Lett ; 12(1): 94, 2020 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-34138120

RESUMO

Semiconducting conjugated polymer nanoparticles (SPNs) represent an emerging class of phototheranostic materials with great promise for cancer treatment. In this report, low-bandgap electron donor-acceptor (D-A)-conjugated SPNs with surface cloaked by red blood cell membrane (RBCM) are developed for highly effective photoacoustic imaging and photothermal therapy. The resulting RBCM-coated SPN (SPN@RBCM) displays remarkable near-infrared light absorption and good photostability, as well as high photothermal conversion efficiency for photoacoustic imaging and photothermal therapy. Particularly, due to the small size (< 5 nm), SPN@RBCM has the advantages of deep tumor penetration and rapid clearance from the body with no appreciable toxicity. The RBCM endows the SPNs with prolonged systematic circulation time, less reticuloendothelial system uptake and reduced immune-recognition, hence improving tumor accumulation after intravenous injection, which provides strong photoacoustic signals and exerts excellent photothermal therapeutic effects. Thus, this work provides a valuable paradigm for safe and highly efficient tumor photoacoustic imaging and photothermal therapy for further clinical translation.

11.
Adv Healthc Mater ; 9(1): e1900996, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31746153

RESUMO

Photodynamic therapy (PDT) usually aggravates tumor hypoxia, which promotes the survival and metastasis of residue cancer cells; furthermore, although PDT-induced immunogenic death of cancer cells can induce host antitumor responses, such responses are generally weak and not enough to eliminate the residue cancer cells. Here, metal-organic framework (MOF)-based nanoparticles to combine PDT, antihypoxic signaling, and CpG adjuvant as an in situ tumor vaccine to boost host anticancer responses after PDT are designed. The MOF-based nanoparticles are self-assembled from H2 TCPP and zirconium ions with hypoxia inducible factor (HIF) signaling inhibitor (ACF) and immunologic adjuvant (CpG) loading, and hyaluronic acid (HA) coating on the surface. The final nanoparticles (PCN-ACF-CpG@HA) can specifically target cancer cells overexpressing CD44 receptor though HA; the aggravated hypoxic survival signaling after PDT can be blocked by ACF to inhibit the HIF-1α induced survival and metastasis. With the help of CpG adjuvant, the tumor associated antigens generated from PDT-based cancer cell destruction can initiate strong antitumor immune responses to eliminate residue cancer cells. Taken together, a novel in situ immunostimulatory strategy is designed to synergistically enhance therapeutic effects of PDT by activating host antitumor immune-responses both in vitro and in vivo, which may have great potential for clinical translation in future.


Assuntos
Adjuvantes Imunológicos/química , Vacinas Anticâncer/imunologia , Estruturas Metalorgânicas/química , Nanopartículas/química , Neoplasias/terapia , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ilhas de CpG , Humanos , Ácido Hialurônico/química , Subunidade alfa do Fator 1 Induzível por Hipóxia/antagonistas & inibidores , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Imunoterapia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Zircônio/química
12.
Adv Healthc Mater ; 8(10): e1801627, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30945472

RESUMO

Tumor microenvironment activated nanodevices have remarkable superiority to enhance therapeutic efficacy and minimize side effects, but their practical applications are dramatically reduced by the low abundance and heterogeneous distribution of specific stimuli at the tumor site. Herein, programmable vesicular nanodevices based on the triblock copolymer containing poly(ethylene glycol) (PEG) and poly(caprolactone) (PCL) with peroxalate esters (PO) as hydrogen peroxide-responsive linkage (PEG-PO-PCL-PO-PEG), are developed for co-delivery of hypoxia-activated prodrug (AQ4N) and glucose oxidase (GOD). The obtained nanodevices (PAG) can be activated by the high level of H2 O2 in tumor microenvironment to improve the permeability of membranes for glucose entrance. Afterward, the oxidation of glucose catalyzed by GOD produces amplified H2 O2 amounts which in turn induce complete destruction of PAG for fast release of AQ4N and GOD. Ultimately, the PAG can exert programmable therapeutic effects from the following aspects: 1) starvation therapy by cutting off the energy supply from glucose through GOD catalysis; 2) oxidative cytotoxicity after H2 O2 amplification; 3) chemotherapy of AQ4N activated by the intensified tumor hypoxia microenvironment after oxygen consumption. The stimuli amplification, controlled drug release, synergistic therapy, and corresponding mechanisms of PAG are demonstrated. Therefore, the presented work could provide significant new insights for cancer treatment.


Assuntos
Peróxido de Hidrogênio/metabolismo , Nanotecnologia/métodos , Microambiente Tumoral , Animais , Antraquinonas/química , Antraquinonas/farmacologia , Antraquinonas/uso terapêutico , Catálise , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Glucose/química , Glucose/metabolismo , Glucose Oxidase/química , Glucose Oxidase/metabolismo , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Camundongos , Camundongos Nus , Nanotecnologia/instrumentação , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Oxirredução , Poliésteres/química , Polietilenoglicóis/química , Pró-Fármacos/química , Pró-Fármacos/farmacologia , Pró-Fármacos/uso terapêutico , Carbonilação Proteica
13.
Chem Sci ; 9(37): 7390-7399, 2018 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-30542542

RESUMO

Although photothermal therapy (PTT) has become a compelling strategy for cancer therapy, few studies concern the physiological consequences of PTT ablation. Herein, we discover that PTT-induced hyperthermia can aggravate tumor hypoxia, which may increase the risk of tumor recurrence and reduce PTT efficacy. We thus integrated the pH/hypoxia-triggered Fe(iii)-banoxantrone (AQ4N) prodrug and semiconducting polymer dots (SPs) for programmable triggered cancer photothermal-chemotherapy. A SP-hybridized mesoporous silica framework, decorated by dopamine and polyethylene glycol, named PPMSF, was synthesized by a simple method, and then served as an efficient photo-absorbing agent (PTA) and drug carrier. Fe(iii)-AQ4N and Mn(ii) were then coordinated with PPMSF (abbreviated Mn-APPMSF) via coordination effects. The nanohybrids exhibited tumor micro-environment pH triggered drug release. Under the irradiation of NIR light, magnetic resonance imaging (MRI) tracked the accumulation of the nanohybrids in tumors which then destroyed tumor cells by local hyperthermia, this can consequently aggravate the tumor hypoxia levels. Intriguingly, the aggravated hypoxia can further enhance the reduction of AQ4N to significantly improve therapeutic efficacy and effectively inhibit tumor growth when compared with traditional PTT. These results indicate the potential of our nanohybrids as a programmable synergistic agent for cancer therapy.

14.
Chem Commun (Camb) ; 54(96): 13599-13602, 2018 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-30451251

RESUMO

We designed novel diketopyrrolopyrrole polymer based nanoparticles (DPP-IID-FA), which exhibited strong light absorption and excellent photothermal conversion in the NIR optical window, and displayed high biocompatibility and photostability. Furthermore, our nanoparticles could be efficiently uptaken by cancer cells and exhibited outstanding anticancer ability both in vitro and in vivo under NIR-II laser irradiation.


Assuntos
Antineoplásicos/uso terapêutico , Nanopartículas/química , Polímeros/uso terapêutico , Pirróis/uso terapêutico , Neoplasias do Colo do Útero/terapia , Animais , Antineoplásicos/síntese química , Antineoplásicos/efeitos da radiação , Antineoplásicos/toxicidade , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Células HeLa , Calefação , Humanos , Raios Infravermelhos , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/efeitos da radiação , Fototerapia/métodos , Polímeros/síntese química , Polímeros/efeitos da radiação , Polímeros/toxicidade , Pirróis/síntese química , Pirróis/efeitos da radiação , Pirróis/toxicidade
15.
Biomater Sci ; 6(7): 1834-1845, 2018 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-29786715

RESUMO

Theranostic nanoprobes integrated with dual-modal imaging and therapeutic functions, such as photodynamic therapy (PDT), have exhibited significant potency in cancer treatments due to their high imaging accuracy and non-invasive advantages for cancer elimination. However, biocompatibility and highly efficient accumulation of these nanoprobes in tumor are still unsatisfactory for clinical application. In this study, a photosensitizer -loaded magnetic nanobead with surface further coated with a layer of cancer cell membrane (SSAP-Ce6@CCM) was designed to improve the biocompatibility and cellular uptake and ultimately achieve enhanced MR/NIR fluorescence imaging and PDT efficacy. Compared with similar nanobeads without CCM coating, SSAP-Ce6@CCM showed significantly enhanced cellular uptake, as evidenced by Prussian blue staining, confocal laser scanning microscopy (CLSM) and flow cytometric analysis. Consequently, SSAP-Ce6@CCM displayed a more distinct MR/NIR imaging ability and more obvious photo-cytotoxicity towards cancer cells under 670 nm laser irradiation. Furthermore, the enhanced PDT effect benefited from the surface coating of cancer cell membrane was demonstrated in SMMC-7721 tumor-bearing mice through tumor growth observation and tumor tissue pathological examination. Therefore, this CCM-disguised nanobead that integrated the abilities of MR/NIR fluorescence dual-modal imaging and photodynamic therapy might be a promising theranostic platform for tumor treatment.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Nanopartículas de Magnetita/química , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/farmacologia , Adsorção , Animais , Transporte Biológico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Membrana Celular/química , Membrana Celular/metabolismo , Clorofilídeos , Humanos , Raios Infravermelhos , Lasers , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Nanopartículas de Magnetita/administração & dosagem , Nanopartículas de Magnetita/ultraestrutura , Camundongos , Camundongos Nus , Imagem Óptica/métodos , Fármacos Fotossensibilizantes/química , Porfirinas/química , Espécies Reativas de Oxigênio/agonistas , Espécies Reativas de Oxigênio/metabolismo , Nanomedicina Teranóstica/métodos , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Biomater Sci ; 6(6): 1457-1468, 2018 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-29770812

RESUMO

Dual and multi-stimuli responsive polymeric nanoparticles that respond to two or more signals can further improve drug release performance compared with nanoparticles that respond to a single stimulus. However, usage of such nanoparticles to deliver siRNA and chemotherapeutic drugs in a sequential manner are currently very rare; meanwhile, this technology is vital to optimize the efficacy of chemotherapy towards cancer cells with multidrug resistance. By loading o-nitrobenzyl ester derivative caged DOX (DOC) into the inner poly(lactic-co-glycolic acid) (PLGA) core and adsorbing siRNA of P-gp protein onto the cationic polymeric shell derived from a disulfide-containing alkyl modified polyethylenimine (C16-S-S-PEI), here, a reduction/photo dual responsive device (RPDRD) is successfully designed for programmed P-gp siRNA and doxorubicin delivery. The dual-stimuli design of the RPDRD allows tumor microenvironment-specific and rapid release of P-gp siRNA triggered by the enrichment of reducing agent glutathione (GSH, up to 10 mM) for reversal of drug resistance by initially suppressing P-gp protein expression in MCF/ADR cells and then selectively triggering drug release by external light for chemotherapy afterwards. The sequential release behavior of P-gp siRNA and DOX can be demonstrated both in vitro and in vivo, thus enhancing the intracellular drug retention and optimizing the chemotherapy efficacy of DOX by silencing P-gp; this strategy may have extensive application prospects in MDR cancer treatment in future.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Neoplasias da Mama/terapia , Preparações de Ação Retardada/química , Doxorrubicina/administração & dosagem , Nanopartículas/química , Polímeros/química , Pró-Fármacos/administração & dosagem , RNA Interferente Pequeno/administração & dosagem , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Animais , Antibióticos Antineoplásicos/farmacocinética , Antibióticos Antineoplásicos/uso terapêutico , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Doxorrubicina/farmacocinética , Doxorrubicina/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Luz , Células MCF-7 , Camundongos Endogâmicos BALB C , Camundongos Nus , Oxirredução , Pró-Fármacos/farmacocinética , Pró-Fármacos/uso terapêutico , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/farmacocinética , RNA Interferente Pequeno/uso terapêutico , Terapêutica com RNAi
17.
ACS Appl Mater Interfaces ; 10(23): 19416-19427, 2018 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-29771490

RESUMO

Prerelease of RNA molecules than chemotherapeutic drugs with a sufficient interval is a vital prerequisite for RNA/drug co-delivery strategy to overcome multidrug resistance (MDR) of cancer cells, but how to precisely control their release at different time points is still a grand challenge up to now. This study aims to on-demand remotely manipulate RNA and drug release in real time through single delivery system to sequentially play their respective roles for optimizing and enhancing their synergistic antitumor effects. To this end, a photoresponsive mesoporous silica nanoparticle (PMSN) is fabricated as a co-delivery vehicle of P-glycoprotein (P-gp) short-hairpin RNA (shRNA) and photocaged prodrug of doxorubicin (DOX), by which the orthogonal and sequential release of shRNA and DOX can be achieved using an external light. In our design, the cationic poly[2-( N, N-dimethylaminoethyl)methacrylate] is introduced onto the PMSN surface through a light-sensitive coumarin ester derivative linker to adsorb P-gp shRNA, whereas the photocleavable o-nitrobenzyl ester derivative-caged DOX is loaded into the inner pores of the PMSN. The PMSN is found to be effectively internalized by MDR cancer cells, and the release of the shRNA and DOX is demonstrated to be independently regulated by 405 and 365 nm light irradiations due to selectively cleaved coumarin and o-nitrobenzyl ester, resulting in enhanced drug retention, and finally bring out optimized and significantly improved chemotherapeutic effects both in vitro and in vivo for MDR cancer treatment, which might hold extensive application prospects in MDR cancer treatment in future.


Assuntos
RNA Interferente Pequeno/química , Membro 1 da Subfamília B de Cassetes de Ligação de ATP , Linhagem Celular Tumoral , Doxorrubicina , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Humanos
18.
Drug Deliv ; 25(1): 353-363, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29366349

RESUMO

Developing multifunctional nanoparticle-based theranostic platform for cancer diagnosis and treatment is highly desirable, however, most of the present theranostic platforms are fabricated via complicated structure/composition design and time-consuming synthesis procedures. Herein, the multifunctional Gd/CeO2-ZrO2/DOX-PEG nanoplatform with single nano-structure was fabricated through a facile route, which possessed MR/CT dual-model imaging and chemotherapy ability. The nanoplatform not only exhibited well-defined shapes, tunable compositions and narrow size distributions, but also presented a well anti-cancer effect and MR/CT imaging ability. Therefore, the Gd/CeO2-ZrO2/DOX-PEG nanoplatform could be applied for chemotherapy as well as dual-model MR/CT imaging.


Assuntos
Doxorrubicina/administração & dosagem , Doxorrubicina/química , Gadolínio/química , Nanopartículas/química , Zircônio/química , Animais , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos/métodos , Feminino , Células Hep G2 , Humanos , Imageamento por Ressonância Magnética/métodos , Camundongos Endogâmicos BALB C , Camundongos Nus , Tamanho da Partícula , Polietilenoglicóis/química , Tomografia Computadorizada por Raios X/métodos
19.
J Mater Chem B ; 6(47): 7889-7897, 2018 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-32255034

RESUMO

Photothermal therapy (PTT) is emerging as a powerful tool for the treatment of cancer. However, typical photothermal agents are excited by conventional near-infrared light (NIR-I, 700-900 nm), which leads to low tissue penetration and significantly hinders their further application. Compared with NIR-I light, the second NIR optical window light (NIR-II, 1000-1700 nm) can remarkably increase the tissue penetration depth; however, photothermal agents in this optical window are extremely limited and need to be further explored. Herein, we prepared Ti2O3 nanoparticles through a ball milling method, and to further improve their biocompatibility and targeting efficiency, the Ti2O3 nanoparticles were modified with hyaluronic acid. The as-prepared nanoparticles exhibited strong light absorption and excellent photothermal conversion efficiency in the NIR-II optical window. Both in vitro and in vivo studies clearly demonstrated that the Ti2O3@HA nanoparticles not only exhibit high biocompatibility and photostability, but also can be efficiently taken up by cancer cells and display excellent anticancer ability in the NIR-II region. Thus, this study provides a novel photothermal agent for PTT in the NIR-II optical window, which may further advance cancer photo-treatment in future.

20.
Nanoscale ; 9(36): 13828, 2017 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-28894871

RESUMO

Correction for 'Folic acid-functionalized up-conversion nanoparticles: toxicity studies in vivo and in vitro and targeted imaging applications' by Lining Sun et al., Nanoscale, 2014, 6, 8878-8883.

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