Near-infrared fluorescence imaging using organic dye nanoparticles

Near-infrared (NIR) fluorescence imaging in the 700–1000 nm wavelength range has been very attractive for early detection of cancers. Conventional NIR dyes often suffer from limitation of low brightness due to self-quenching, insufficient photo- and bioenvironmental stability, and small Stokes shift. Herein, we present a strategy of using small-molecule organic dye nanoparticles (ONPs) to encapsulate NIR dyes to enable efficient fluorescence resonance energy transfer to obtain NIR probes with remarkably enhanced performance for in vitro and in vivo imaging. In our design, host ONPs are used as not only carriers to trap and stabilize NIR dyes, but also light-harvesting agent to transfer energy to NIR dyes to enhance their brightness. In comparison with pure NIR dyes, our organic dye nanoparticles possess almost 50-fold increased brightness, large Stokes shifts (∼250 nm) and dramatically enhanced photostability. With surface modification, these NIR-emissive organic nanoparticles have water-dispersity and size- and fluorescence- stability over pH values from 2 to 10 for almost 60 days. With these superior advantages, these NIR-emissive organic nanoparticles can be used for highly efficient folic-acid aided specific targeting in vivo and ex vivo cellular imaging. Finally, during in vivo imaging, the nanoparticles show negligible toxicity. Overall, the results clearly display a potential application of using the NIR-emissive organic nanoparticles for in vitro and in vivo imaging.     

PEGylated dendrimer-entrapped gold nanoparticles for in vivo blood pool and tumor imaging by computed tomography

We report the synthesis and characterization of dendrimer-entrapped gold nanoparticles (Au DENPs) modified by polyethylene glycol (PEG) with enhanced biocompatibility for computed tomography (CT) imaging applications. In this study, amine-terminated poly(amidoamine) dendrimers of generation 5 (G5.NH₂) modified by PEG monomethyl ether (G5.NH₂-mPEG₂₀) were used as templates to synthesize Au DENPs, followed by acetylation of the remaining dendrimer terminal amines to generate PEGylated Au DENPs. The partial PEGylation modification of dendrimer terminal amines allows high loading of Au within the dendrimer interior, and consequently by simply varying the Au salt/dendrimer molar ratio, the size of the PEGylated Au DENPs can be controlled at a range of 2-4 nm with a narrow size distribution. The formed PEGylated Au DENPs are water-dispersible, stable in a pH range of 5-8 and a temperature range of 0-50 °C, and non-cytotoxic at a concentration as high as 100 μm. X-ray absorption coefficient measurements show that the attenuation intensity of the PEGylated Au DENPs is much higher than that of Omnipaque with iodine concentration similar to Au. With the sufficiently long half-decay time demonstrated by pharmacokinetics studies, the PEGylated Au DENPs enabled not only X-ray CT blood pool imaging of mice and rats after intravenous injection of the particles, but also effective CT imaging of a xenograft tumor model in nude mice. These findings suggest that the designed PEGylated Au DENPs can be used as a promising contrast agent with enhanced biocompatibility for CT imaging of various biological systems, especially in cancer diagnosis.     

NIR photothermal therapy using polyaniline nanoparticles

Developing a biocompatible and efficient photothermal coupling agent with appropriate size is a prerequisite for the development of near-infrared (NIR) light-induced photothermal therapy (PTT). In the present study, polyaniline nanoparticles (PANPs) with a size of 48.5 ± 1.5 nm were fabricated and exhibited excellent dispersibility in water by a hydrothermal method and further surface functionalization by capping with F127. The developed F127-modified PANPs (F-PANPs) had a high molar extinction coefficient of 8.95 × 10⁸ m⁻¹ cm⁻¹, and high NIR photothermal conversion efficiency of 48.5%. Furthermore, combined with NIR irradiation at 808 nm and injection of F-PANP samples, in vivo photothermal ablation of tumor with excellent treatment efficacy was achieved. In vitro transmission electron microscopy (TEM) images of cells, methyl thiazolyl tetrazolium (MTT) assay, histology, and hematology studies revealed that the F-PANPs exhibit low toxicity to living systems. Therefore, F-PANPs could be used as PTT agents for ablating cancer, and the concept of developing polyaniline-based nanoparticles can serve as a platform technology for the next generation of in vivo PTT agents.     

Intracellular redox-activated anticancer drug delivery by functionalized hollow mesoporous silica nanoreservoirs with tumor specificity

In this study, a type of intracellular redox-triggered hollow mesoporous silica nanoreservoirs (HMSNs) with tumor specificity was developed in order to deliver anticancer drug (i.e., doxorubicin (DOX)) to the target tumor cells with high therapeutic efficiency and reduced side effects. Firstly, adamantanamine was grafted onto the orifices of HMSNs using a redox-cleavable disulfide bond as an intermediate linker. Subsequently, a synthetic functional molecule, lactobionic acid-grafted-β-cyclodextrin (β-CD-LA), was immobilized on the surface of HMSNs through specific complexation with the adamantyl group, where β-CD served as an end-capper to keep the loaded drug within HMSNs. β-CD-LA on HMSNs could also act as a targeting agent towards tumor cells (i.e., HepG2 cells), since the lactose group in β-CD-LA is a specific ligand binding with the asialoglycoprotein receptor (ASGP-R) on HepG2 cells. In vitro studies demonstrated that DOX-loaded nanoreservoirs could be selectively endocytosed by HepG2 cells, releasing therapeutic DOX into cytoplasm and efficiently inducing the apoptosis and cell death. In vivo investigations further confirmed that DOX-loaded nanoreservoirs could permeate into the tumor sites and actively interact with tumor cells, which inhibited the tumor growth with the minimized side effect. On the whole, this drug delivery system exhibits a great potential as an efficient carrier for targeted tumor therapy in vitro and in vivo.     

Mesoporous NaYbF4@NaGdF4 core-shell up-conversion nanoparticles for targeted drug delivery and multimodal imaging

We developed a facile strategy to obtain a new kind of mesoporous core-shell structured up-conversion nanoparticles (mUCNPs), composed of a NaYbF₄:2%Er core and a mesoporous NaGdF₄ shell. This mesoporous shell not only enhanced the up-conversion luminescence but also endowed many other functionalities of the nanoparticles such as drug delivery and bio-imaging capabilities. Moreover, after being conjugated with polyethylenimine (PEI) and folic acid (FA), core-shell mUCNPs exhibited good water dispersibility, enhanced drug delivery efficiency, and remarkable targeting ability to cancer cells. To certify the folate receptors (FR)-mediated targeted drug delivery, cell viability assay, cell up-conversion luminescence imaging and flow cytometry analysis were carried out. Furthermore, apart from the application for targeted drug delivery, the as-prepared core-shell mUCNPs could also be employed as the contrast agents for X-ray computed tomography (CT) and magnetic resonance (MR) imaging, because of the strong X-ray attenuation ability of Yb and high longitudinal molar relaxivity (r₁) of Gd in the nanoparticles, providing the potential for simultaneously bio-imaging and cancer-targeting therapy.     

Amphiphilic micelles of poly(2-methyl-2-carboxytrimethylene carbonate-co-D,L-lactide)-graft-poly(ethylene glycol) for anti-cancer drug delivery to solid tumours

Drug delivery to solid tumours remains a challenge because both tumour physiology and drug solubility are unfavourable. Engineered materials can provide the basis for drug reformulation, incorporating active compounds and modulating their pharmacokinetic and biodistribution behaviour. To this end, we encapsulated docetaxel, a poorly soluble taxane drug, in a self-assembled polymeric nanoparticle micelle of poly(2-methyl-2-carboxytrimethylene carbonate-co-d,l-lactide)-graft-poly(ethylene glycol) (poly(TMCC-co-LA)-g-PEG). This formulation was compared with its conventional ethanolic polysorbate 80 formulation in terms of plasma circulation and biodistribution in an orthotopic mouse model of breast cancer. Notably, the polymeric nanoparticle formulation achieved greater tumour retention, resulting in prolonged exposure of cancer cells to the active drug. This behaviour was unique to the tumour tissue. The active drug was eliminated at equal or greater rates in all other tissues assayed when delivered in the polymeric nanoparticles vs. the free drug formulation. Thus, these polymeric nanoparticles are promising vehicles for solid tumour drug delivery applications, offering greater tumour exposure while eliminating the need for toxic solvents and surfactants in the dosing formulation.     

Multifunctional nanoparticles for upconversion luminescence/MR multimodal imaging and magnetically targeted photothermal therapy

Theranostics, the combination of diagnostics and therapies, has become a new concept in the battles with various major diseases such as cancer. Herein, we develop multifunctional nanoparticles (MFNPs) with highly integrated functionalities including upconversion luminescence, superparamagnetism, and strong optical absorption in the near-infrared (NIR) region with high photostability. In vivo dual modal optical/magnetic resonance imaging of mice uncovers that by placing a magnet nearby the tumor, MFNPs tend to migrate toward the tumor after intravenous injection and show high tumor accumulation, which is ∼8 folds higher than that without magnetic targeting. NIR laser irradiation is then applied to the tumors grown on MFNP-injected mice under magnetic tumor-targeting, obtaining an outstanding photothermal therapeutic efficacy with 100% of tumor elimination in a murine breast cancer model. We present here a strategy for multimodal imaging-guided, magnetically targeted physical cancer therapy and highlight the promise of using multifunctional nanostructures for cancer theranostics.     

Pluronic-encapsulated natural chlorophyll nanocomposites for in vivo cancer imaging and photothermal/photodynamic therapies

A great challenge in developing nanotechnologies for cancer diagnosis and therapy has been the combined functionalities required for complicated clinical procedures. Among all requirements, toxicity has been the major hurdle that has prevented most of the nano-carriers from clinical use. Here, we extracted chlorophyll (Chl) from vegetable and encapsulated it into polymer (pluronic F68, Plu) micelles for cancer imaging and therapy. The results showed that the Chl-containing nanocomposites were capable of mouse tumor targeting, and the nanocomposite fluorescence within the tumor sites remained at high intensity more than two days after tail-vein injection. It is interesting that oral administration with the nanocomposites was also successful for tumor target imaging. Furthermore, the dietary Chl was found to be able to efficiently convert near-infrared laser irradiation to heat. The growths of melanoma cells and mouse tumors were effectively inhibited after being treated with the nanocomposites and irradiation. The suppression of the tumors was achieved by laser-triggered photothermal and photodynamic synergistic effects of Chl. As a natural substance from vegetable, Chl is non-toxic, making it an ideal nano-carrier for cancer diagnosis and treatment. Based on the results of this research, the Plu–Chl nanocomposites have shown promise for future clinical applications.     

LaB6 nanoparticles with carbon-doped silica coating for fluorescence imaging and near-IR photothermal therapy of cancer cells

In this study, LaB₆ nanoparticles are used as a novel nanomaterial for near-infrared (NIR) photothermal therapy because they are cheaper than nanostructured gold, are easy to prepare and have an excellent NIR photothermal conversion property. Furthermore, the surface of LaB₆ nanoparticles is coated with a carbon-doped silica (C-SiO₂) shell to introduce a fluorescent property and improve stability and biocompatibility. The resulting LaB₆@C-SiO₂ nanoparticles retain the excellent NIR photothermal conversion property and exhibit a bright blue emission under UV irradiation or a green emission under visible irradiation. Using a HeLa cancer cell line, it is demonstrated that LaB₆@C-SiO₂ nanoparticles have no significant cytotoxicity, but their presence leads to remarkable cell death after NIR irradiation. In addition, from the observation of cellular uptake, the fluorescence labeling function of LaB₆@SiO₂ (LaB₆ core/SiO₂ shell) nanoparticles is also confirmed. These results suggest that LaB₆@C-SiO₂ nanoparticles may potentially serve as an efficient multifunctional nano-platform for simultaneous fluorescent imaging and NIR-triggered photothermal therapy of cancer cells.     

铕掺杂氧化钆纳米颗粒的核磁共振成像与荧光标记应用探究

目的制备双模态造影剂铕掺杂氧化钆（Gd2O3：Eu3＋）纳米颗粒,探究其应用于核磁共振成像（MRI）及荧光标记的可行性。方法通过液体环境激光烧蚀固体Gd203：Eun靶材,得到Gd2O3：Eu3＋胶体纳米颗粒,通过透射电镜观察该纳米材料形貌特征：S18细胞增殖MTF实验表征其生物毒性;3．0T磁共振成像系统观察其在体外和Balb／c裸鼠体内鼻咽癌S18裸鼠移植瘤的显像特点：荧光显微镜观察其在细胞内荧光标记效果。结果液体环境激光熔蚀技术制备的纳米颗粒分散性良好。平均粒径为7．2nm;材料生物毒性低;体外MRI成像呈明显梯度;将该材料尾静脉注射裸鼠后约30min．鼻咽癌S18裸鼠移植瘤信号强度逐渐增高;细胞与纳米颗粒共同培养4h后,荧光显微镜显示纳米颗粒被细胞吞噬并发出红色荧光。结论成功研制了分散性良好,生物毒性低的双模态造影剂Gd2O3：Eu3＋并将其应用与小鼠体内MRI成像和细胞荧光成像．得到了良好的成像效果,为结合MRI与荧光成像技术提供一种途径。     

Targeting hepatocyte growth factor receptor (Met) positive tumor cells using internalizing nanobody-decorated albumin nanoparticles

The hepatocyte growth factor receptor (HGFR, c-Met or Met) is a receptor tyrosine kinase that is involved in embryogenesis, tissue regeneration and wound healing. Abnormal activation of this proto-oncogene product is implicated in the development, progression and metastasis of many cancers. Current therapies directed against Met, such as ligand- or, dimerization-blocking antibodies or kinase inhibitors, reduce tumor growth but hardly eradicate the tumor. In order to improve anti-Met therapy, we have designed a drug delivery system consisting of crosslinked albumin nanoparticles decorated with newly selected anti-Met nanobodies (anti-Met-NANAPs). The anti-Met NANAPs bound specifically to and were specifically taken up by Met-expressing cells and transported to lysosomes for degradation. Treatment of tumor cells with anti-Met NANAPs also resulted in downregulation of the total Met protein. This study shows that anti-Met NANAPs offer a potential system for lysosomal delivery of drugs into Met-positive tumor cells.     

基于荧光反射成像的小鼠下肢外周组织的灌注参数成像

目的：利用荧光反射成像技术,重建出小鼠下肢外周组织的灌注参数的分布图像。方法BALB/c裸鼠尾静脉注射10μg的吲哚菁绿（ICG）溶液,给药后立即用荧光反射成像系统连续拍摄ICG荧光强度图像,总计时长200 s。随后拍取小鼠轮廓的白光图,以获得感兴趣区域（ROI）。用双指数模型对ROI区域的动态荧光数据建模分析,重建出小鼠下肢外周组织的灌注参数图像。结果利用双指数模型获得的荧光强度-时间曲线与测量的灌注曲线接近,并重建出反映小鼠下肢外周组织血液灌注情况的参数分布图。结论提出一种量化分析小鼠下肢外周组织血液灌注状态的方法,重建的灌注参数图像分辨率较高。该方法采用非入侵式活体成像,对实验对象损伤小。     

In vivo tumor-targeted dual-modal fluorescence/CT imaging using a nanoprobe co-loaded with an aggregation-induced emission dye and gold nanoparticles

As an intensely studied computed tomography (CT) contrast agent, gold nanoparticle has been suggested to be combined with fluorescence imaging modality to offset the low sensitivity of CT. However, the strong quenching of gold nanoparticle on fluorescent dyes requires complicated design and shielding to overcome. Herein, we report a unique nanoprobe (M-NPAPF-Au) co-loading an aggregation-induced emission (AIE) red dye and gold nanoparticles into DSPE-PEG₂₀₀₀ micelles for dual-modal fluorescence/CT imaging. The nanoprobe was prepared based on a facile method of “one-pot ultrasonic emulsification”. Surprisingly, in the micelles system, fluorescence dye (NPAPF) efficiently overcame the strong fluorescence quenching of shielding-free gold nanoparticles and retained the crucial AIE feature. In vivo studies demonstrated the nanoprobe had superior tumor-targeting ability, excellent fluorescence and CT imaging effects. The totality of present studies clearly indicates the significant potential application of M-NPAPF-Au as a dual-modal non-invasive fluorescence/X-ray CT nanoprobe for in vivo tumor-targeted imaging and diagnosis.     

Magnetically engineered Cd-free quantum dots as dual-modality probes for fluorescence/magnetic resonance imaging of tumors

Magnetically engineered Cd-free CuInS₂@ZnS:Mn quantum dots (QDs) were designed, synthesized, and evaluated as potential dual-modality probes for fluorescence and magnetic resonance imaging (MRI) of tumors in vivo. The synthesis of Mn-doped core–shell structured CuInS₂@ZnS mainly comprised three steps, i.e., the preparation of fluorescent CuInS₂ seeds, the particle surface coating of ZnS, and the Mn-doping of the ZnS shells. Systematic spectroscopy studies were carried out to illustrate the impacts of ZnS coating and the following Mn-doping on the optical properties of the QDs. In combination with conventional fluorescence, fluorescence excitation, and time-resolved fluorescence measurements, the structure of CuInS₂@ZnS:Mn QDs prepared under optimized conditions presented a Zn gradient CuInS₂ core and a ZnS outer shell, while Mn ions were mainly located in the ZnS shell, which well balanced the optical and magnetic properties of the resultant QDs. For the following in vivo imaging experiments, the hydrophobic CuInS₂@ZnS:Mn QDs were transferred into water upon ligand exchange reactions by replacing the 1-dodecanethiol ligand with dihydrolipoic acid-poly(ethylene glycol) (DHLA-PEG) ligand. The MTT assays based on HeLa cells were carried out to evaluate the cytotoxicity of the current Cd-free CuInS₂@ZnS:Mn QDs for comparing with that of water soluble CdTe QDs. Further in vivo fluorescence and MR imaging experiments suggested that the PEGylated CuInS₂@ZnS:Mn QDs could well target both subcutaneous and intraperitoneal tumors in vivo.     

Inhibition of orthotopic osteosarcoma growth and metastasis by multitargeted antitumor activities of pigment epithelium-derived factor

Osteosarcoma is major cause of cancer-related death in the pediatric age group, and this is due to the development of pulmonary metastases that fail to be eradicated with current treatment regimes. Although there have been significant improvements in the long-term survival of such patients, 25–50% with initially non-metastatic disease, subsequently develop metastases and this remains the major cause of death for these patients. In this study, we report the multimodal activity of pigment epithelium-derived factor (PEDF) in inhibiting osteosarcoma growth, angiogenesis and metastasis. In vitro, we found that administration of recombinant PEDF (rPEDF) on two osteosarcoma cell lines (rat UMR 106-01 and human SaOS-2) significantly reduced tumor cell proliferation and increased apoptosis, as well as decreased cell invasion, angiogenesis, and increased adhesion to collagen type-1. Administration of rPEDF upregulated the mRNA expression of phenotypic osteoblast differentiation markers (ALP, pro-α₁ collagen and osteocalcin) in a pre-osteoblastic cell line, UMR 201, and also increased mineralized nodule formation in both UMR 106-01 and SaOS-2. In vivo, rPEDF dramatically suppressed primary osteosarcoma growth and the development of macroscopic pulmonary metastases in an orthotopic model of human osteosarcoma (SaOS-2). Interestingly, no activity was seen in tumors grown subcutaneously, suggesting a paracrine interaction between PEDF and the bone microenvironment. Preliminary pharmacoevaluation studies demonstrated rPEDF stability within media containing serum and osteosarcoma cells, and no gross systemic toxicity was observed in vivo with rPEDF administration. These results suggest that PEDF is emerging as an attractive and clinically appealing drug candidate for the treatment of osteosarcoma The authors declare that they have no competing financial interests.     

Polyethyleneimine-mediated synthesis of folic acid-targeted iron oxide nanoparticles for in vivo tumor MR imaging

We report a facile polyethyleneimine (PEI)-mediated approach to synthesizing folic acid (FA)-targeted magnetic iron oxide nanoparticles (Fe₃O₄ NPs) for in vivo magnetic resonance (MR) imaging of tumors. In this study, stable PEI-coated Fe₃O₄ NPs were prepared by a one-pot hydrothermal route. The aminated Fe₃O₄ NPs with PEI coating enabled covalent conjugation of fluorescein isothiocyanate (FI) and folate-conjugated polyethylene glycol (PEG) with one end of carboxyl groups (FA-PEG-COOH). Followed by final acetylation, FA-targeted PEGylated Fe₃O₄ NPs (Fe₃O₄-PEI-Ac-FI-PEG-FA NPs) were formed. The formed multifunctional Fe₃O₄ NPs were characterized via different techniques. We show that the PEI-mediated approach along with the PEGylation conjugation enables the generation of water-dispersible and stable multifunctional Fe₃O₄ NPs, and the particles are quite cytocompatible and hemocompatible in the given concentration range as confirmed by in vitro cytotoxicity assay, cell morphology observation, and hemolysis assay. In addition, flow cytometry and confocal microscopy data show that the multifunctional Fe₃O₄ NPs are able to target a model cancer cell line (KB cells) overexpressing FA receptors in vitro. Importantly, the FA-targeted Fe₃O₄ NPs are able to be used as an efficient nanoprobe for MR imaging of cancer cells in vitro and a xenografted tumor model in vivo via an active FA targeting pathway. With the facile PEI-mediated formation strategy and PEGylation conjugation chemistry, the Fe₃O₄ NPs may be multifunctionalized with other biological ligands for MR imaging of different biological systems.     

Visualization of nascent tumor angiogenesis in lung and liver metastasis by differential dual-color fluorescence imaging in nestin-linked-GFP mice

Nestin regulatory-element-driven green fluorescent protein (ND-GFP) transgenic mice highly express GFP in proliferating endothelial cells and nascent blood vessels. In the present study, we visualized angiogenesis in experimental lung and liver metastases by GFP imaging in the ND-GFP transgenic mice. The murine melanoma cell line, B16F10 expressing red fluorescent protein (RFP), was injected i.v. in ND-GFP mice. ND-GFP was highly expressed in proliferating nascent blood vessels in the tumors that developed in the lung after tail vein injection, and in the tumors that developed in the liver after portal vein injection of RFP-expressing melanoma cells. Liver metastasis and angiogenesis were imaged intravitally. Doxorubicin significantly decreased metastatic angiogenesis in the liver. These results demonstrate a new imageable model of angiogenesis in metastasis in the liver and the lung. This new model should enable further understanding of the onset of angiogenesis in metastasis and its effect on metastatic growth. The model will serve as a unique screen for inhibitors of angiogenesis of metastatic tumors. The fact that liver-metastasis angiogenesis can be imaged in the live animal enables real-time studies of the effect of angiogenesis inhibitors.     

Enhanced intracellular translocation and biodistribution of gold nanoparticles functionalized with a cell-penetrating peptide (VG-21) from vesicular stomatitis virus

Reduced toxicity and ease of modification make gold nanoparticles (GNPs) suitable for targeted delivery, bioimaging and theranostics by conjugating cell-penetrating peptides (CPPs). This study presents the biodistribution and enhanced intracellular uptake of GNPs functionalized with VG-21, a CPP derived from vesicular stomatitis virus glycoprotein (G). Cell penetrating efficiency of VG-21 was demonstrated using CellPPD web server, conjugated to GNPs and were characterized using, UV-visible and FTIR spectroscopy, transmission electron microscopy, dynamic light scattering and zeta potential. Uptake of VG-21 functionalized GNPs (fGNPs) was tested in eukaryotic cell lines, HEp-2, HeLa, Vero and Cos-7, using flow cytometry, fluorescence and transmission electron microscopy (TEM), and inductively coupled plasmon optical emission spectroscopy (ICP-OES). The effects of nanoparticles on stress and toxicity related genes were studied in HEp-2 cells. Cytokine response to fGNPs was studied in vitro and in vivo. Biodistribution of nanoparticles was studied in BALB/c mice using TEM and ICP-OES. VG-21, GNPs and fGNPs had little to no effect on cell viability. Upon exposure to fGNPs, HEp-2 cells revealed minimal down regulation of stress response genes. fGNPs displayed higher uptake than GNPs in all cell lines with highest internalization by HEp-2, HeLa and Cos-7 cells, in endocytotic vesicles and nuclei. Cytokine ELISA showed that mouse J774 cells exposed to fGNPs produced less IL-6 than did GNP-treated macrophage cells, whereas TNF-α levels were low in both treatment groups. Biodistribution studies in BALB/c mice revealed higher accumulation of fGNPs than GNPs in the liver and spleen. Histopathological analyses showed that fGNP-treated mice accumulated 35 ng/mg tissue and 20 ng/mg tissue gold in spleen and liver respectively, without any adverse effects. Likewise, serum cytokines were low in both GNP- and fGNP-treated mice. Thus, VG-21-conjugated GNPs have enhanced cellular internalization and are suitable for various biomedical applications as nano-conjugates.     

酶响应性纳米粒子治疗肿瘤:纳米粒子积累和药物释放的优势

背景:基于纳米药物递送系统在肿瘤中增强的渗漏与滞留效应,以设计对刺激产生响应的抗肿瘤药物递送载体是最近肿瘤治疗策略发展的一大方向.酶响应性纳米递送系统是其中重要的组成部分,以肿瘤特异性高表达的酶作为精准靶向目标,大幅提高靶向性能.目的:总结近年来肿瘤治疗研究中酶响应性纳米粒子的设计思路、靶向效率及抗肿瘤效果.方法:检索...