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Rheumatoid arthritis (RA) is an autoimmune disease with multifactorial etiology and intricate pathogenesis. In RA, repeated monotherapy is frequently associated with inadequate efficacy, drug resistance, and severe side effects. Therefore, a shift has occurred in clinical practice toward combination therapy. However, conventional combination therapy encounters several hindrances, including low selectivity to arthritic joints, short half-lives, and varying pharmacokinetics among coupled drugs. Emerging nanotechnology offers an incomparable opportunity for developing advanced combination therapy against RA. First, it allows for co-delivering multiple drugs with augmented physicochemical properties, targeted delivery capabilities, and controlled release profiles. Second, it enables therapeutic nanomaterials development, thereby expanding combination regimens to include multifunctional nanomedicines. Lastly, it facilitates the construction of all-in-one nanoplatforms assembled with multiple modalities, such as phototherapy, sonodynamic therapy, and imaging. Thus, nanotechnology offers a promising solution to the current bottleneck in both RA treatment and diagnosis. This review summarizes the rationale, advantages, and recent advances in nano-empowered combination therapy for RA. It also discusses safety considerations, drug-drug interactions, and the potential for clinical translation. Additionally, it provides design tips and an outlook on future developments in nano-empowered combination therapy. The objective of this review is to achieve a comprehensive understanding of the mechanisms underlying combination therapy for RA and unlock the maximum potential of nanotechnology, thereby facilitating the smooth transition of research findings from the laboratory to clinical practice.
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Artrite Reumatoide , Humanos , Artrite Reumatoide/tratamento farmacológico , Animais , Nanomedicina/métodos , Nanotecnologia/métodos , Terapia Combinada , Antirreumáticos/uso terapêutico , Sistemas de Liberação de Medicamentos/métodos , Nanoestruturas/química , Nanoestruturas/uso terapêutico , Nanopartículas/químicaRESUMO
Breast cancer with triple-negative subtype (TNBC) presents significant challenges with limited treatment options and a poorer prognosis than others. While PD-1/PD-L1 checkpoint inhibitors have shown promise, their efficacy in TNBC remains constrained. In recent years, nanoparticle (NP) technologies offer a novel approach to enhance cancer therapy by optimizing the tumor microenvironment and augmenting chemo- and immunotherapy effects in various preclinical and clinical settings. This review discusses recent investigations in NP strategies for improving PD-1/PD-L1 blockade-based combination therapy for TNBC. Those include single or multi-therapeutic NPs designed to enhance immunogenicity of the tumor, induce immunogenic cell death, and target immunosuppressive elements within the tumor microenvironment. The investigations also include NPs co-loaded with PD-L1 inhibitors and other therapeutic agents, leveraging targeted delivery and synergistic effects to maximize efficacy while minimizing systemic toxicity. Overall, NP approaches represent a promising avenue for enhancing PD-1/PD-L1 checkpoint blockade-based combination therapy in TNBC and encourage further developmental studies.
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Preclinical models of cancer are vital for assessing and predicting efficacies and toxicities of novel treatments prior to testing in human subjects. Current pancreatic tumor models exhibit variable growth rates, unpredictable tumor size after implantation in non-native tissues, or require surgical implantation. Surgical implantation in the pancreas may produce not only unpredictable tumor uptake but could also elicit additional inflammatory responses. In searching for a pancreatic carcinoma cell that can be introduced into a mouse via simple injection, we found that Pan02, a murine ductal pancreatic adenocarcinoma derived from a pancreatic lesion of a C57BL/6 mouse, inoculated peritoneally can consistently produce pancreatic tumors. This intraperitoneal, but not intravenous, introduction of Pan02 cells leads to the attachment and growth of Pan02 in the pancreas before spreading to other tissues. Time-course tissue analysis indicates that the Pan02 cells first find, infiltrate, and grow within the pancreas, producing a pancreatic tumor model. This model appears to mimic pancreatic cancer development in humans and is the first reported use of Pan02 cells to produce orthotopic pancreatic and metastatic neoplasms in a mouse model without the need for tumor implantation within matrices or survival surgeries. This orthotopic pancreatic tumor model, with consistent tumor uptake, synchronized tumor development and survival, and predictable outcomes may enable and accelerate the preclinical evaluation of treatment candidates for pancreatic cancer.
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Adenocarcinoma , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Camundongos , Animais , Neoplasias Pancreáticas/patologia , Adenocarcinoma/patologia , Camundongos Endogâmicos C57BL , Carcinoma Ductal Pancreático/patologia , Pâncreas/patologia , Modelos Animais de Doenças , Linhagem Celular TumoralRESUMO
Leukemia remains incurable partly due to difficulties in reaching and maintaining therapeutic drug concentrations in the target tissues and cells. Next-generation drugs targeted to multiple cell checkpoints, including the orally active venetoclax (Bcl-2 target) and zanubrutinib (BTK target), are effective and have improved safety and tolerability compared to conventional, nontargeted chemotherapies. However, dosing with a single agent frequently leads to drug resistance; asynchronous coverage due to the peak-and-trough time-course of two or more oral drugs has prevented drug combinations from simultaneously knocking out the respective drugs' targets for sustained leukemia suppression. Higher doses of the drugs may potentially overcome asynchronous drug exposure in leukemic cells by saturating target occupancy, but higher doses often cause dose-limiting toxicities. To synchronize multiple drug target knockout, we have developed and characterized a drug combination nanoparticle (DcNP), which enables the transformation of two short-acting, orally active leukemic drugs, venetoclax and zanubrutinib, into long-acting nanoformulations (VZ-DCNPs). VZ-DCNPs exhibit synchronized and enhanced cell uptake and plasma exposure of both venetoclax and zanubrutinib. Both drugs are stabilized by lipid excipients to produce the VZ-DcNP nanoparticulate (d ~ 40 nm) product in suspension. The VZ-DcNP formulation has enhanced uptake of the two drugs (VZ) in immortalized leukemic cells (HL-60), threefold over that of its free drug counterpart. Additionally, drug-target selectivity of VZ was noted with MOLT-4 and K562 cells that overexpress each target. When given subcutaneously to mice, the half-lives of venetoclax and zanubrutinib were extended by approximately 43- and 5-fold, respectively, compared to an equivalent free VZ. Collectively, these data suggest that VZ in VZ-DcNP warrant consideration for preclinical and clinical development as a synchronized and long-acting drug-combination for the treatment of leukemia.
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The assessment of the biodegradability of nanomaterials is of pragmatic importance for understanding the interactions between nanomaterials and biological systems and for the determination of ultimate fate of these materials as well as their potential use. We recently developed carbon-based biconcave nanodisks (CBBNs) serving as a versatile nanocarrier for enhanced accumulation in tumors and combined photothermal-chemotherapy. Here, we investigate both the enzymatic and cellular degradation of CBBNs by monitoring their cellular response with electron microscopy, near-infrared absorbance spectroscopy, and cell viability and oxidative stress assessments. Our results show that CBBNs underwent significant degradation in solutions catalyzed by horseradish peroxidase (HRP) and hydrogen peroxide (H2O2), or in the presence of macrophage cells. The ability of CBBNs to be degraded in biological systems provides suitability for their future biomedical applications.
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Despite advances in breast cancer treatments and related 5-year survival outcomes, metastatic breast cancer cures remain elusive. The current standard of care includes a combination of surgery, radiation therapy and drug therapy. However, even the most advanced procedures and treatments do not prevent breast cancer recurrence and metastasis. Once metastasis occurs, patient prognosis is poor. Recent elucidation of the spatiotemporal transit of metastatic cancer cells from primary tumor sites to distant sites provide an opportunity to integrate knowledge of drug disposition in our effort to enhance drug localization and exposure in cancer laden tissues . Novel technologies have been developed, but could be further refined to facilitate the distribution of drugs to target cancer cells and tissues. The purpose of this review is to highlight the challenges in metastatic breast cancer treatment and focus on novel drug combination and nanotechnology approaches to overcome the challenges. With improved definition of metastatic tissue target, directed localization and retention of multiple, pharmacologically active drugs to tissues and cells of interest may overcome the limitations in breast cancer treatment that may lead to a cure for breast cancer.
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Neoplasias da Mama , Nanopartículas , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Feminino , Humanos , Nanopartículas/uso terapêutico , Nanotecnologia/métodos , Recidiva Local de NeoplasiaRESUMO
Understanding the basic interactions between engineered nanoparticles (ENPs) and biological systems is essential for evaluating ENPs' safety and developing better nanomedicine. Profound interactions between ENPs and biomolecules such as proteins are inevitable to occur when ENPs are administered or exposed to biological systems, for example, through intravenous injection, oral, or respiration. As a key component of these interactions, protein corona (PC) is immediately formed surrounding the outlayer of ENPs. PC formation is crucial because it gives ENPs a new biological identity by altering not only the physiochemical properties, but also the biobehaviors of ENPs. In the past two decades, most investigations about PC formation were carried out with in vitro systems which could not represent the true events occurring within in vivo systems. Most recently, studies of in vivo PC formation were reported, and it was found that the protein compositions and structures were very different from those formed in vitro. Herein, we provide an in-time review of the recent investigations of this in vivo PC formation of ENPs. In this review, commonly used characterization methods and compositions of in vivo PC are summarized firstly. Next, we highlight the impacts of the in vivo PC formation on absorption, blood circulation, biodistribution, metabolism, and toxicity of administered ENPs. We also introduce the applications of modulating in vivo PC formation in nanomedicine. We further discuss the challenges and future perspectives.
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Despite the availability of molecularly targeted treatments such as antibodies and small molecules for human epidermal growth factor receptor 2 (HER2), hormone receptor (HR), and programmed death-ligand 1 (PD-L1), limited treatment options are available for advanced metastatic breast cancer (MBC), which constitutes ~90% mortality. Many of these monotherapies often lead to drug resistance. Novel MBC-targeted drug-combination therapeutic approaches that may reduce resistance are urgently needed. We investigated intercellular adhesion molecule-1 (ICAM-1), which is abundant in MBC, as a potential target to co-localize two current drug combinations, gemcitabine (G) and paclitaxel (T), assembled in a novel drug-combination nanoparticle (GT DcNP) form. With an ICAM-1-binding peptide (referred to as LFA1-P) coated on GT DcNPs, we evaluated the role of the LFA1-P density in breast cancer cell localization in vitro and in vivo. We found that 1-2% LFA1-P peptide incorporated on GT DcNPs provided optimal cancer cell binding in vitro with ~4× enhancement compared to non-peptide GT DcNPs. The in vivo probing of GT DcNPs labeled with a near-infrared marker, indocyanine green, in mice by bio-imaging and G and T analyses indicated LFA1-P enhanced drug and GT DcNP localization in breast cancer cells. The target/healthy tissue (lung/gastrointestinal (GI)) ratio of particles increased by ~60× compared to the non-ligand control. Collectively, these data indicated that LFA1 on GT DcNPs may provide ICAM-1-targeted G and T drug combination delivery to advancing MBC cells found in lung tissues. As ICAM-1 is generally expressed even in breast cancers that are triple-negative phenotypes, which are unresponsive to inhibitors of nuclear receptors or HER2/estrogen receptor (ER) agents, ICAM-1-targeted LFA1-P-coated GT DcNPs should be considered for clinical development to improve therapeutic outcomes of MBCs.
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The ability to visualize and quantify apoptosis in vivo is critical to monitoring the disease response to treatment and providing prognostic information. However, the application of current apoptosis labeling probes faces significant challenges including nonspecific tissue uptake, inefficient apoptotic cell labeling and short monitoring windows. Here we report a highly specific apoptosis labeling nanoparticle (NP) probe with Pisum sativum agglutinin (PSA) as a tumor targeting ligand for prolonged in vivo apoptosis imaging. The NP (namely, IONP-Neu-PSA) consists of a magnetic iron oxide core (IONP) conjugated with PSA, and a reporter fluorophore. IONP-Neu-PSA demonstrated minimal cytotoxicity and high labeling specificity towards apoptotic cells in vitro. When applied in vivo, IONP-Neu-PSA tracks apoptotic tumors for a prolonged period of two weeks under near-IR imaging with low background noise. Moreover, IONP-Neu-PSA possesses T2 contrast enhancing properties that can potentially enable apoptosis detection by magnetic resonance imaging (MRI). The high specificity for apoptotic cells, sustained fluorescence signals, and non-invasive imaging capability exhibited by IONP-Neu-PSA make it a versatile tool for cancer treatment monitoring and pathological research.
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Nanopartículas , Preparações Farmacêuticas , Apoptose , Compostos Férricos , Imageamento por Ressonância MagnéticaRESUMO
PURPOSE: To develop drug-combination nanoparticles (DcNPs) composed of hydrophilic gemcitabine (G) and hydrophobic paclitaxel (T) and deliver both drugs to metastatic cancer cells. METHODS: GT DcNPs were evaluated based on particle size and drug association efficiency (AE%). The effect of DcNP on GT plasma time-course and tissue distribution was characterized in mice and a pharmacokinetic model was developed. A GT distribution study into cancer nodules (derived from 4 T1 cells) was performed. RESULTS: An optimized GT DcNP composition (d = 59.2 nm ±9.2 nm) was found to be suitable for IV formulation. Plasma exposure of G and T were enhanced 61-fold and 3.8-fold when given in DcNP form compared to the conventional formulation, respectively. Mechanism based pharmacokinetic modeling and simulation show that both G and T remain highly associated to DcNPs in vivo (G: 98%, T:75%). GT DcNPs have minimal distribution to healthy organs with selective distribution and retention in tumor burdened tissue. Tumor bearing lungs had a 5-fold higher tissue-to-plasma ratio of gemcitabine in GT DcNPs compared to healthy lungs. CONCLUSIONS: DcNPs can deliver hydrophilic G and hydrophobic T together to cancer nodules and produce long acting exposure, likely due to stable GT association to DcNPs in vivo.
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Neoplasias da Mama/tratamento farmacológico , Desoxicitidina/análogos & derivados , Combinação de Medicamentos , Nanopartículas/administração & dosagem , Metástase Neoplásica/tratamento farmacológico , Paclitaxel/farmacocinética , Animais , Desoxicitidina/sangue , Desoxicitidina/farmacocinética , Sistemas de Liberação de Medicamentos/métodos , Feminino , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Paclitaxel/sangue , Baço/efeitos dos fármacos , Distribuição Tecidual/efeitos dos fármacos , GencitabinaRESUMO
Early diagnosis along with new drugs targeted to cancer receptors and immunocheckpoints have improved breast cancer survival. However, full remission remains elusive for metastatic breast cancer due to dose-limiting toxicities of heavily used, highly potent drug combinations such as gemcitabine and paclitaxel. Therefore, novel strategies that lower the effective dose and improve safety margins could enhance the effect of these drug combinations. To this end, we developed and evaluated a novel drug combination of gemcitabine and paclitaxel (GT). Leveraging a simple and scalable drug-combination nanoparticle platform (DcNP), we successfully prepared an injectable GT combination in DcNP (GT DcNP). Compared to a Cremophor EL/ethanol assisted drug suspension in buffer (CrEL), GT DcNP exhibits about 56-fold and 8.6-fold increases in plasma drug exposure (area under the curve, AUC) and apparent half-life of gemcitabine respectively, and a 2.9-fold increase of AUC for paclitaxel. Using 4T1 as a syngeneic model for breast cancer metastasis, we found that a single GT (20/2 mg/kg) dose in DcNP nearly eliminated colonization in the lungs. This effect was not achievable by a CrEL drug combination at a 5-fold higher dose (i.e., 100/10 mg/kg GT). A dose-response study indicates that GT DcNP provided a therapeutic index of ~15.8. Collectively, these data suggest that GT DcNP could be effective against advancing metastatic breast cancer with a margin of safety. As the DcNP formulation is intentionally designed to be simple, scalable, and long-acting, it may be suitable for clinical development to find effective treatment against metastatic breast cancer.
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Antineoplásicos/química , Antineoplásicos/farmacologia , Neoplasias da Mama/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Nanopartículas/química , Animais , Antineoplásicos/sangue , Antineoplásicos/uso terapêutico , Linhagem Celular , Desoxicitidina/análogos & derivados , Desoxicitidina/sangue , Desoxicitidina/química , Desoxicitidina/farmacologia , Desoxicitidina/uso terapêutico , Relação Dose-Resposta a Droga , Composição de Medicamentos , Sinergismo Farmacológico , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Paclitaxel/sangue , Paclitaxel/química , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Resultado do Tratamento , GencitabinaRESUMO
Gadolinium (Gd)-based chelates are used as clinical T1 contrast agents for magnetic resonance imaging (MRI) due to their demonstrated high sensitivity and positive contrast enhancement capability. However, there has been an increasing safety concern about their use in medicine because of the toxicity of the metal ions released from these contrast agents when used in vivo. Although significant effort has been made in developing metal-free MRI contrast agents, none have matched the magnetic properties achieved by the gold standard clinical contrast agent, Gd diethylene penta-acetic acid (Gd-DTPA). Here, we report the development of a single-layer, boron-doped graphene quantum dot (termed SL-BGQD) that demonstrates better T1 contrast enhancement than Gd-DTPA. The SL-BGQD is shown to provide significantly higher positive contrast enhancement than the Gd-DTPA contrast agent in imaging vital organs, including kidneys, liver, and spleen, and especially, vasculatures. Further, our results show that the SL-BQGD is able to bypass the blood-brain barrier and allows sustained imaging for at least one hour with a single injection. Hematological and histopathological analyses show that the SL-BGQD demonstrates a non-toxic profile in wild-type mice and may, therefore, serve as an improved, safer alternative to currently available clinical MRI contrast agents.
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Meios de Contraste/química , Imageamento por Ressonância Magnética/métodos , Pontos Quânticos/química , Animais , Barreira Hematoencefálica/metabolismo , Boro , Meios de Contraste/normas , Diagnóstico por Imagem/métodos , Diagnóstico por Imagem/normas , Grafite , Humanos , CamundongosRESUMO
Gold nanoparticles through nucleation of Au clusters have been extensively studied. However, due to low potency, prolonged tissue retention, and irreversible accumulation, the safety considerations have limited their therapeutic and diagnostic applications. Novel gold nanostructures with retained physical properties and higher biodegradability could be prepared by alternative approaches. Previously, a lipid nanoparticle (LNP) platform carrying gadolinium (Gd3+) has been reported to eliminate through the biliary without accumulation in the liver or kidney within 24 h. Inspired by this discovery, we investigated a new approach of forming gold nanoparticles using preformed LNPs grafting diethylenetriamine-pentaacetic acid as a chelating agent. Tiny Au nanoparticles are formed by simply mixing Au3+ with preformed diethylenetriamine-pentaacetic acid-LNP. The Au3+ associates stably to these LNPs after a systematic optimization. The Au-grafted LNPs are scalable and showed excellent photothermal effects when subjected to near-infrared light irradiation. They exhibit enhanced light-induced tumor cell killing at higher efficiency, compared with that of classical gold nanoparticles (citrated reduced). Given an additional small dose (2 Gy) of gamma irradiation, Au-grafted LNP could produce synergistic photothermal and radiotherapeutic effects under reduced light dose. The simple and adaptive nanoparticle design may enhance the margin of safety of gold nanoparticles in the treatment of cancers and other diseases.
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Produtos Biológicos , Nanopartículas Metálicas , Linhagem Celular Tumoral , Quelantes , Ouro , LipídeosRESUMO
Systemic delivery of hydrophobic anti-cancer drugs with nanocarriers, particularly for drug-resistant and metastatic cancer, remain a challenge because of the difficulty to achieve high drug loading, while maintaining a small hydrodynamic size and colloid stability in blood to ensure delivery of an efficacious amount of drug to tumor cells. Here we introduce a new approach to address this challenge. In this approach, nanofibers of larger size with good drug loading capacity are first constructed by a self-assembly process, and upon intravascular injection and interacting with serum proteins in vivo, these nanofibers break down into ultra-fine nanoparticles of smaller size that inherit the drug loading property from their parent nanofibers. We demonstrate the efficacy of this approach with a clinically available anti-cancer drug: paclitaxel (PTX). In vitro, the PTX-loaded nanoparticles enter cancer cells and induce cellular apoptosis. In vivo, they demonstrate prolonged circulation in blood, induce no systemic toxicity, and show high potency in inhibiting tumor growth and metastasis in both mouse models of aggressive, drug-resistant breast cancer and melanoma. This study points to a new strategy toward improved anti-cancer drug delivery and therapy.
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Intratumoral hypoxia is a major contributor to multiple drug resistance (MDR) in cancer, and can lead to poor prognosis of patients receiving chemotherapy. Development of an MDR-inhibitor that mitigates the hypoxic environment is crucial for cancer management and treatment. Reported is a biocompatible and biodegradable catalase-conjugated iron oxide nanoparticle (Cat-IONP) capable of converting reactive oxygen species to molecular oxygen to supply an oxygen source for the hypoxic tumor microenvironment. Cat-IONP demonstrates initial enzymatic activity comparable to free catalase while providing a nearly threefold increase in long-term enzymatic activity. It is demonstrated that Cat-IONP significantly reduces the in vitro expression of hypoxia-inducible factors at the transcription level in a breast cancer cell line. Co-treatment of Cat-IONP and paclitaxel (PTX) significantly increases the drug sensitivity of hypoxic-cultured cells, demonstrating greater than twofold and fivefold reduction in cell viability in comparison to cells treated only with 80 and 120 × 10-6 m PTX, respectively. These findings demonstrate the ability of Cat-IONP to act as an MDR-inhibitor at different biological levels, suggesting a promising strategy to combat cancer-MDR and to optimize cancer management and treatment outcomes.
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Neoplasias da Mama/terapia , Catalase/química , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Compostos Férricos/química , Hipóxia , Nanopartículas Metálicas/química , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Feminino , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Camundongos , Estresse Oxidativo , Paclitaxel/farmacologia , Espectroscopia de Infravermelho com Transformada de Fourier , Resultado do TratamentoRESUMO
Fluorescence imaging of biological systems in the second near-infrared window (NIR-II) has recently drawn much attention because of its negligible background noise of autofluorescence and low tissue scattering. Here we present a new NIR-II fluorescent agent, graphene quantum dots dual-doped with both nitrogen and boron (N-B-GQDs). N-B-GQDs have an ultra-small size (~ 5 nm), are highly stable in serum, and demonstrate a peak fluorescent emission at 1000 nm and high photostability. In addition to the NIR-II imaging capability, N-B-GQDs efficiently absorb and convert NIR light into heat when irradiated by an external NIR source, demonstrating a photothermal therapeutic effect that kills cancer cells in vitro and completely suppresses tumor growth in a glioma xenograft mouse model. N-B-GQDs demonstrate a safe profile, prolonged blood half-life, and rapid excretion in mice, which are the characteristics favorable for in vivo biomedical applications.
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It is considered a significant challenge to construct nanocarriers that have high drug loading capacity and can overcome physiological barriers to deliver efficacious amounts of drugs to solid tumors. Here, the development of a safe, biconcave carbon nanodisk to address this challenge for treating breast cancer is reported. The nanodisk demonstrates fluorescent imaging capability, an exceedingly high loading capacity (947.8 mg g-1 , 94.78 wt%) for doxorubicin (DOX), and pH-responsive drug release. It exhibits a higher uptake rate by tumor cells and greater accumulation in tumors in a mouse model than its carbon nanosphere counterpart. In addition, the nanodisk absorbs and transforms near-infrared (NIR) light to heat, which enables simultaneous NIR-responsive drug release for chemotherapy and generation of thermal energy for tumor cell destruction. Notably, this NIR-activated dual therapy demonstrates a near complete suppression of tumor growth in a mouse model of triple-negative breast cancer when DOX-loaded nanodisks are administered systemically.
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Carbono/química , Sistemas de Liberação de Medicamentos/métodos , Hipertermia Induzida/métodos , Nanoestruturas/química , Fotoquimioterapia/métodos , Animais , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/farmacocinética , Antibióticos Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Terapia Combinada , Doxorrubicina/química , Doxorrubicina/farmacocinética , Doxorrubicina/farmacologia , Feminino , Raios Infravermelhos , Camundongos , Camundongos Endogâmicos BALB C , Nanoestruturas/efeitos da radiação , Nanoestruturas/ultraestrutura , Distribuição TecidualRESUMO
Nanostructured materials that have low tissue toxicity, multi-modal imaging capability and high photothermal conversion efficiency have great potential to enable image-guided near infrared (NIR) photothermal therapy (PTT). Here, we report a bifunctional nanoparticle (BFNP, â¼16â¯nm) comprised of a magnetic Fe3O4 core (â¼9.1â¯nm) covered by a fluorescent carbon shell (â¼3.4â¯nm) and prepared via a one-pot solvothermal synthesis method using ferrocene as the sole source. The BFNP exhibits excitation wavelength-tunable, upconverted and near-infrared (NIR) fluorescence property due to the presence of the carbon shell, and superparamagnetic behavior resulted from the Fe3O4 core. BFNPs demonstrate dual-modal imaging capacity both in vitro and in vivo with fluorescent imaging excited under a varying wavelength from 405â¯nm to 820â¯nm and with T2-weighted magnetic resonance imaging (r2â¯=â¯264.76â¯mM-1â¯s-1). More significantly, BFNPs absorb and convert NIR light to heat enabling photothermal therapy as demonstrated mice bearing C6 glioblastoma. These BFNPs show promise as an advanced nanoplatform to provide imaging guided photothermal therapy.