上转换光动力诊疗体系的构建及抗癌研究进展

具有创伤小、毒性低、选择性好、无耐药性等优点的光动力疗法已被广泛应用于癌症治疗研究。然而,多数光敏剂存在水溶性差易聚集、肿瘤组织选择性差的问题,且其激发光都在可见或紫外光范围内,组织穿透深度较浅导致治疗深度不够,限制了光动力疗效。稀土上转换纳米粒子具有低生物毒性、高化学稳定性、强组织穿透力等优点,可作为将近红外光转换成紫外/可见光的发光材料和光敏剂载体,因此,构建上转换光动力诊疗体系为增强光动力疗效提供新思路。本文介绍了上转换光动力诊疗体系的构建方法,包括物理吸附法、物理包封法、共价偶联法,并分析了其应用于光动力抗癌研究的优缺点,最后总结并展望了其存在的挑战及未来发展方向。     

刺激响应型多肽的研究及其在肿瘤诊疗中的应用

多肽因其独特的理化性能,如生物相容性好,合成修饰方法简单易行,功能多样化和生物体内响应性高等优点,已被广泛用于构建刺激响应型肿瘤诊疗体系.这种以刺激响应型多肽为基础构建的药物诊疗体系,能够在到达肿瘤以前保持药物的零释放,而在靶向到达肿瘤组织后,在肿瘤组织特殊微环境或是外源刺激下(如肿瘤特异性表达酶的刺激、p H刺激和氧化还原刺激等),实现药物的精准靶向释放同时释放出各种诊疗信号.这种具有特异性刺激响应型的多肽载体可以最大程度的提高药物的抗肿瘤效果,降低药物的毒副作用,以及提高肿瘤诊断的精准度.本文简要综述了近年来不同刺激响应型多肽在肿瘤诊疗领域的研究进展.     

基于上转换纳米颗粒的光动力疗法研究新进展

作为一种新型治疗手段,光动力疗法近年来被广泛应用于癌症等疾病的治疗研究.然而,用于激活光敏剂的紫外或可见光具有较低的组织穿透深度,限制了光动力疗法的治疗效果.上转换纳米颗粒可以将组织穿透能力较强的近红外光转换为紫外或可见光,为实现近红外光激活的光动力疗法提供了光转换器,有望解决传统光动力疗法组织穿透深度较浅的问题.本文...     

以上转换纳米颗粒和光动力疗法为基础的肿瘤联合治疗研究进展

光动力疗法作为一种非侵入性治疗手段已广泛应用于肿瘤的临床治疗。然而其疗效却深受紫外-可见光组织穿透深度的限制。镧系掺杂上转换纳米颗粒可以将近红外光转换为紫外-可见光,被广泛用于与传统光敏剂结合实现更为高效的光动力治疗。近年来,以上转换纳米颗粒和光动力疗法为基础的肿瘤联合治疗研究备受关注,本文重点介绍了该领域的最新研究进展,并对其未来发展方向作出了展望。     

基于肿瘤微环境响应的DNA纳米结构递药系统

DNA分子由于其独特的生物相容性和可编程性,在增强药物靶向性和降低药物毒性方面展现了独特的优势和巨大的潜力。随着人们对肿瘤微环境研究的深入和环境响应性的DNA触发器的研制,近些年已报道了许多基于肿瘤微环境响应的DNA纳米结构递药系统,这些DNA纳米结构递药系统结合了纳米运载工具良好的生物分布和药代动力学特性,以及小型药物载体的快速扩散和渗透特性。通过靶向广泛的肿瘤栖息地而不是肿瘤特异性受体,该策略有可能克服肿瘤异质性问题,并可用于设计诊断和治疗多种实体肿瘤的纳米颗粒。在体内能够稳定地转运,在肿瘤组织独特的微环境刺激下释放药物,能有效地控制药物释放部位和释放速度,极大地降低了肿瘤治疗的毒副作用。本文主要从pH响应型、GSH响应型、ATP响应型、酶响应型、抗原响应型五个方面,综述了基于肿瘤微环境响应的DNA纳米结构递药系统的最新研究进展,分类介绍了这些DNA纳米载体的设计策略和响应释放机制,此外,还重点介绍了该领域面临的前景和挑战。     

肿瘤微环境响应药物递送系统的设计

化学药物治疗(化疗)是目前临床上治疗肿瘤最有效的方法之一,但传统的给药方式导致药物对肿瘤的靶向性差、药物利用率低.在杀伤肿瘤细胞的同时,化疗药物对人体正常细胞也有很大的损伤,因此在化疗过程中通常伴随着严重的副作用,例如恶心、呕吐以及脱发等.随着肿瘤学和纳米材料的迅速发展,多种纳米药物载体被应用于肿瘤的治疗.纳米药物载体...     

光和温度刺激响应型材料

刺激响应型材料是一类在环境因素刺激下,自身的某些物理或化学性质发生相应变化的材料。刺激因素包括光、温度、pH、离子强度、电场和磁场等。本文综述了近年来光和温度刺激响应型材料的研究进展,主要从光响应型水凝胶和光致变色材料的结构类型及应用概述了光响应型材料的发展;同时从温度响应型水凝胶、热致形状记忆材料和热敏变色材料几方面介绍了温度响应型材料的研究进展及应用,并展望了光和温度刺激响应型材料在多学科领域的应用前景。     

基于cypate光裂解的新型近红外光响应稀土上转换纳米载药系统※

光响应药物释放体系具有非侵入性、远程可控且时空分辨率高等特点, 在杀菌、抗癌等生物医学领域具有重要应用价值. 但目前近红外光响应的光裂解药物递送体系报道较少且光响应效率还有待提高. 本工作将稀土纳米颗粒包覆介孔二氧化硅, 逐步偶联近红外染料cypate、金刚烷胺和β-环糊精来封堵孔口, 利用cypate的自敏光氧化断键作为光响应开关, 成功构建了一种新型近红外光响应稀土上转换纳米载药系统. 该纳米载药系统负载抗生素氧氟沙星表现出极低的药物流失率和较高的808 nm光照释放效率, 并且通过控制光照时间可以满足不同的给药量需求. 体外抗菌实验结果进一步验证了该纳米载药系统的光响应药物释放性能. 此外, 该纳米载药系统在980 nm激光激发下的上转换发光较强且不影响药物释放, 可以实现纳米载药系统的药物定位和生物成像功能. 本研究为发展高效光响应载药体系提供了新的思路.     

聚合物纳米光诊疗剂的制备与应用新进展

共轭聚合物纳米颗粒是由π-共轭有机聚合物组成的尺寸在1~100nm范围内的新型有机纳米材料。与传统的有机小分子、半导体量子点和无机纳米材料相比,聚合物纳米颗粒具有光学性质特殊、结构多样、表面易修饰和生物相容性好等优点,因而被广泛应用于生物成像、传感与检测、载药和治疗等领域。本文主要围绕聚合物纳米颗粒的制备方法、性质结构和生物相容性等方面,重点介绍了聚合物纳米颗粒作为光诊疗剂在荧光成像、光声成像,以及光动力和光热治疗领域的研究进展,并对聚合物纳米颗粒的发展前景和未来面临的挑战进行了探讨。     

内源性刺激响应策略在肿瘤精准诊疗中的应用

肿瘤微环境具有低pH值、乏氧、高谷胱甘肽含量、过表达酶以及氧化应激增加等系列异常特征.这些内源性差异在肿瘤增殖、侵袭、迁移以及新生血管生成等环节发挥重要作用,同时也为肿瘤精准诊疗提供了机遇.开发内源性刺激响应型诊疗剂已成为肿瘤精准诊疗领域的研究热点.该文综述了近年来发展的各类内源性刺激响应型诊疗体系的设计原理及其在肿瘤...     

Exploiting a New Approach to Destroy the Barrier of Tumor Microenvironment: Nano-Architecture Delivery Systems

Recent findings suggest that tumor microenvironment (TME) plays an important regulatory role in the occurrence, proliferation, and metastasis of tumors. Different from normal tissue, the condition around tumor significantly altered, including immune infiltration, compact extracellular matrix, new vasculatures, abundant enzyme, acidic pH value, and hypoxia. Increasingly, researchers focused on targeting TME to prevent tumor development and metastasis. With the development of nanotechnology and the deep research on the tumor environment, stimulation-responsive intelligent nanostructures designed based on TME have attracted much attention in the anti-tumor drug delivery system. TME-targeted nano therapeutics can regulate the distribution of drugs in the body, specifically increase the concentration of drugs in the tumor site, so as to enhance the efficacy and reduce adverse reactions, can utilize particular conditions of TME to improve the effect of tumor therapy. This paper summarizes the major components and characteristics of TME, discusses the principles and strategies of relevant nano-architectures targeting TME for the treatment and diagnosis systematically.     

纳米材料在肿瘤光动力治疗中的研究进展

光动力治疗是新兴的非侵入性癌症治疗方法。纳米材料以其独特的结构以及光物理、光化学性质成为可用于光动力治疗的光敏剂。根据纳米材料的不同种类,分别对无机非金属纳米材料、无机金属纳米材料、有机小分子纳米材料以及有机聚合物纳米材料等的构建策略及其在光动力治疗肿瘤中的应用进行综述。展望了纳米材料在未来肿瘤光动力治疗中的挑战和发展方向。为新一代纳米光敏剂的构建提供创新思路,并扩展其在癌症治疗中的潜力。     

Openwork@Dendritic Mesoporous Silica Nanoparticles for Lactate Depletion and Tumor Microenvironment Regulation

The direct depletion of lactate accumulated in the tumor microenvironment holds promise for cancer therapy but remains challenging. Herein, we report a one-pot synthesis of openwork@ dendritic mesoporous silica nanoparticles (ODMSNs) to address this problem. ODMSNs self-assembled through a time-resolved lamellar growth mechanism feature an openworked core and a dendritic shell, both constructed by silica nanosheets of ≈3 nm. With a large pore size, high surface area and pore volume, ODMSNs exhibited a high loading capacity (>0.7 g g⁻¹) of lactate oxidase (LOX) and enabled intratumoral lactate depletion by >99.9 %, leading to anti-angiogenesis, down-regulation of vascular endothelial growth factor, and increased tumor hypoxia. The latter event facilitates the activation of a co-delivered prodrug for enhancing anti-tumor and anti-metastasis efficacy. This study provides an innovative nano-delivery system and demonstrates the first example of direct lactate-depletion-enabled chemotherapy.     

A Near-Infrared Photo-Switched MicroRNA Amplifier for Precise Photodynamic Therapy of Early-Stage Cancers

Stimuli-responsive photodynamic therapy (PDT) is a hot topic in precise medicine, but the low abundance of responsive trigger molecules in early-stage disease limits application. Here we designed an amplifier with multiple upconversion luminances to achieve a near-infrared photo-switched cascade reaction triggered by specific microRNA and precise PDT of early-stage cancers. This amplifier was composed of photo-caged DNA nanocombs and an upconversion nanoparticle (UCNP) sensitized with IRDye 800CW. The nanocomb was prepared by assembling a photozipper-protected hairpin and two kinds of hybridizable hairpin probes on a DNA skeleton. Upon 808-nm light irradiation, the produced UV light cleaved off the photozipper to induce microRNA-responsive cascade hybridization reaction, activating the photosensitizers linked to different hairpins to generate reactive oxygen species (ROS) under the simultaneously emitted blue light for efficient PDT.     

Hypoxia Induced by Upconversion‐Based Photodynamic Therapy: Towards Highly Effective Synergistic Bioreductive Therapy in Tumors

Local hypoxia in tumors is an undesirable consequence of photodynamic therapy (PDT), which will lead to greatly reduced effectiveness of this therapy. Bioreductive pro‐drugs that can be activated at low‐oxygen conditions will be highly cytotoxic under hypoxia in tumors. Based on this principle, double silica‐shelled upconversion nanoparticles (UCNPs) nanostructure capable of co‐delivering photosensitizer (PS) molecules and a bioreductive pro‐drug (tirapazamine, TPZ) were designed (TPZ‐UC/PS), with which a synergetic tumor therapeutic effect has been achieved first by UC‐based (UC‐) PDT under normal oxygen environment, immediately followed by the induced cytotoxicity of activated TPZ when oxygen is depleted by UC‐PDT. Treatment with TPZ‐UC/PS plus NIR laser resulted in a remarkably suppressed tumor growth as compared to UC‐PDT alone, implying that the delivered TPZ has a profound effect on treatment outcomes for the much‐enhanced cytotoxicity of TPZ under PDT‐induced hypoxia.     

SnSe Nanosheets Mimic Lactate Dehydrogenase to Reverse Tumor Acid Microenvironment Metabolism for Enhancement of Tumor Therapy

The acidic tumor microenvironment (TME) is unfriendly to the activity and function of immune cells in the TME. Here, we report inorganic nanozymes (i.e., SnSe NSs) that mimic the catalytic activity of lactate dehydrogenase to degrade lactate to pyruvate, contributing to the metabolic treatment of tumors. As found in this study, SnSe NSs successfully decreased lactate levels in cells and tumors, as well as reduced tumor acidity. This is associated with activation of the immune response of T cells, thus alleviating the immunosuppressive environment of the TME. More importantly, the nanozyme successfully inhibited tumor growth in mutilate mouse tumor models. Thus, SnSe NSs show a promising result in lactate depletion and tumor suppression, which exemplifies its potential strategy in targeting lactate for metabolic therapy.     

Nd3+‐Sensitized Upconversion Metal–Organic Frameworks for Mitochondria‐Targeted Amplified Photodynamic Therapy

Herein, we report the design and synthesis of a mitochondria‐specific, 808 nm NIR light‐activated photodynamic therapy (PDT) system based on the combination of metal–organic frameworks (MOFs) and upconversion photochemistry with an organelle‐targeting strategy. The system was synthesized through the growth of a porphyrinic MOF on Nd³⁺‐sensitized upconversion nanoparticles to achieve Janus nanostructures with further asymmetric functionalization of the surface of the MOF domain. The PDT nanoplatform allows for photosensitizing with 808 nm NIR light, which could effectively avoid the laser‐irradiation‐induced overheating effect. Furthermore, mitochondria‐targeting could amplify PDT efficacy through the depolarization of the mitochondrial membrane and the initiation of intrinsic apoptotic pathway. This work sheds light on the hybrid engineering of MOFs to combat their current limitations for PDT.