Photo-responsive NIR-II biomimetic nanomedicine for efficient cancer-targeted theranostics

In pancreatic cancer, the special barrier system formed by a large number of stromal cells severely hinders drug penetration in deep tumor tissues, resulting in low treatment efficiency. Cell membrane protein-camouflaged liposomal nanomedicines have cancer cell targeting abilities, whereas near-infrared two-zone (NIR-II) fluorescence imaging can achieve deep tissue penetration due to its long light wavelength (1,000–1,700 nm). To combine the cell membrane-based biomimetic technology with NIR-II fluorescence imaging, we constructed a biomimetic nanomedicine (BLIPO-I/D) by camouflaging indocyanine green-doxorubicin (ICG-DOX) liposomes with SW1990 pancreatic cancer cell membrane. The nanomedicine exhibited light-controlled DOX release and high pancreatic cancer treatment efficiency in vitro and in vivo. BLIPO-I/D showed the ability of targeted delivery of a large number of liposomes to pancreatic tumor tissues through homologous targeting of SW1990 cell membranes, which increased the NIR-II fluorescence imaging intensity. Irradiation of the liposomes taken up by pancreatic tumor tissues with near-infrared light (808 nm) triggered the rapid release of DOX from the liposomes, induced the photothermal and photodynamic effects of ICG, which exerted anti-tumor effects. Therefore, the fabricated biomimetic liposomal nanomedicine BLIPO-I/D is expected to achieve precise theranostics of pancreatic cancer.     

Iron oxide nanoparticles-loaded hyaluronic acid nanogels for MRI-aided Alzheimer's disease theranostics

Despite eye-opening advances in developing novel therapeutics for hard-to-treat diseases, treatment of Alzheimer's disease (AD) is still known as the challenge of generations. By the way, scrutinizing and shedding light on a major cause of AD, i.e., fibrillation of β amyloid (Aβ) peptides, have paved the way to find an effective therapy for this life-threatening disease in the foreseeable future. In this study, we endeavored to push forward with research on AD therapy, even as much as an inch, by fabricating and evaluating a theranostic system based on iron oxide nanoparticles-loaded hyaluronic acid nanogels (Fe₃O₄-HyA NGs). Fe₃O₄ nanoparticles were fabricated via a facile co-precipitation method and were loaded in HyA NGs in situ by formation of NGs using a thiolated HyA (HyA-SH) precursor. Standard structural analysis was performed on Fe₃O₄-HyA NGs, and the results revealed the NGs were negatively charged, which led to relatively poor adsorption of plasma proteins, and sized at the range of 120–150 nm. Also, Fe₃O₄-HyA NGs showed a superparamagnetic property with a magnetic saturation of about 62.8 emu/g indicating the successful loading of Fe₃O₄ nanoparticles. Besides, findings of the cytotoxicity analysis could primarily show the NGs did not pose a noticeable risk to normal astrocyte cells (i.e., 96.7% cell viability at 100 µg/ml after 48 h treatment). Moreover, in vitro magnetic resonance imaging (MRI) analysis could reveal the noticeable potential ability of the Fe₃O₄-HyA NGs to generate negative contrast by reducing both T2-weighted and T2*-weighted MR signal intensities with a relaxation rate (r₂) of about 120.87 (1/mM.sec). Finally, Fe₃O₄-HyA NGs exhibited a potential ability to impede Aβ aggregation by around 44% at 10 µM; also, they could induce disaggregation of Aβ fibrils by about 13% at 10 µM. Hence, Fe₃O₄-HyA NGs could be a promising choice for AD theranostics and could be further scrutinized in vitro and in vivo.     

Recent Strategies to Develop Polysaccharide‐Based Nanomaterials for Biomedical Applications

Polysaccharides are abundant in nature, renewable, nontoxic, and intrinsically biodegradable. They possess a high level of functional groups including hydroxyl, amino, and carboxylic acid groups. These functional groups can be utilized for further modification of polysaccharides with small molecules, polymers, and crosslinkers; the modified polysaccharides have been used as effective building blocks in fabricating novel biomaterials for various biomedical applications such as drug delivery carriers, cell‐encapsulating biomaterials, and tissue engineering scaffolds. This review describes recent strategies to modify polysaccharides for the development of polysaccharide‐based biomaterials; typically self‐assembled micelles, crosslinked microgels/nanogels, three‐dimensional hydrogels, and fibrous meshes. In addition, the outlook is briefly discussed on the important aspects for the current and future development of polysaccharide‐based biomaterials, particularly tumor‐targeting intracellular drug delivery nanocarriers.

     

Activatable molecular agents for cancer theranostics

Theranostics that integrates diagnosis and treatment modalities has attracted great attention due to its abilities of personalized therapy and real-time monitoring of therapeutic outcome. Such a theranostic paradigm requires agents to simultaneously possess the capabilities of targeting, imaging, and treatment. Activatable molecular agents (AMAs) are promising for cancer theranostics, as they show a higher signal-to-noise ratio (SNR), real-time detection of cancer-associated biomarkers, lower normal tissue toxicity, and a higher therapeutic effect. This perspective summarizes the recent advancements of AMAs, which include imaging-guided chemotherapy, imaging-guided photodynamic therapy, and imaging-guided photothermal therapy. The molecular design principles, theranostic mechanisms, and biomedical applications of AMAs are described, followed by a discussion of potential challenges of AMAs in cancer theranostics.

Activatable molecualr agents that intergrate diagnosis and treatment modalities have attracted great attention due to its abilities of personalized therapy and real-time monitoring of therapeutic outcome.     

Rational Design and Development of Polymeric Nanogels as Protein Carriers

Proteins have gained significant attention as potential therapeutic agents owing to their high specificity and reduced toxicity. Nevertheless, their clinical utility is hindered by inherent challenges associated with stability during storage and after in vivo administration. To overcome these limitations, polymeric nanogels (NGs) have emerged as promising carriers. These colloidal systems are capable of efficient encapsulation and stabilization of protein cargoes while improving their bioavailability and targeted delivery. The design of such delivery systems requires a comprehensive understanding of how the synthesis and formulation processes affect the final performance of the protein. This review highlights critical aspects involved in the development of NGs for protein delivery, with specific emphasis on loading strategies and evaluation techniques. For example, factors influencing loading efficiency and release kinetics are discussed, along with strategies to optimize protein encapsulation through protein-carrier interactions to achieve the desired therapeutic outcomes. The discussion is based on recent literature examples and aims to provide valuable insights for researchers working toward the advancement of protein-based therapeutics.     

Accessing lipophilic ligands in dendrimer-based amphiphilic supramolecular assemblies for protein-induced disassembly

Supramolecular nanoassemblies that respond to the presence of proteins are of great interest, as aberrations in protein concentrations represent the primary imbalances found in a diseased state. We present here a molecular design, syntheses, and study of facially amphiphilic dendrimers that respond to the presence of the protein, immunoglobulin G. It is of particular interest that the ligand functionality, utilized for causing the binding-induced disassembly, be lipophilic. Demonstration of binding with lipophilic ligands greatly expands the repertoire of binding-induced disassembly, since this covers a rather large class of ligand moieties designed for proteins and these provide specific insights into the mechanistic pathways that are available for the binding-induced disassembly process. Here, we describe the details of the binding induced disassembly, including the change in size of the assembly in response to proteins, concurrent release of noncovalently encapsulated guest molecules, and the specificity of the disassembly process.     

Polymeric Nanogels with Tailorable Degradation Behavior

The aim of this study is to design a polymeric nanogel system with tailorable degradation behavior. To this end, hydroxyethyl methacrylate‐oligoglycolates‐derivatized poly(hydroxypropyl methacrylamide) (pHPMAm‐Gly‐HEMA) and hydroxyethyl methacrylamide‐oligoglycolates‐derivatized poly(hydroxyethyl methacrylamide) (pHEMAm‐Gly‐HEMAm) are synthesized and characterized. pHEMAm‐Gly‐HEMAm shows faster hydrolysis rates of both carbonate and glycolate esters than the same ester groups of pHPMAm‐Gly‐HEMA. pHEMAm‐Gly‐HEMAm nanogels have tailorable degradation kinetics from 24 h to more than 4 d by varying their crosslink densities. It is shown that the release of a loaded macromolecular model drug is controlled by degradation of nanogels. The nanogels show similar cytocompatibility as PLGA nanoparticles and are therefore considered to be attractive systems for drug delivery.

     

Application of Dendrimers in Anticancer Diagnostics and Therapy

The application of dendrimeric constructs in medical diagnostics and therapeutics is increasing. Dendrimers have attracted attention due to their compact, spherical three-dimensional structures with surfaces that can be modified by the attachment of various drugs, hydrophilic or hydrophobic groups, or reporter molecules. In the literature, many modified dendrimer systems with various applications have been reported, including drug and gene delivery systems, biosensors, bioimaging contrast agents, tissue engineering, and therapeutic agents. Dendrimers are used for the delivery of macromolecules, miRNAs, siRNAs, and many other various biomedical applications, and they are ideal carriers for bioactive molecules. In addition, the conjugation of dendrimers with antibodies, proteins, and peptides allows for the design of vaccines with highly specific and predictable properties, and the role of dendrimers as carrier systems for vaccine antigens is increasing. In this work, we will focus on a review of the use of dendrimers in cancer diagnostics and therapy. Dendrimer-based nanosystems for drug delivery are commonly based on polyamidoamine dendrimers (PAMAM) that can be modified with drugs and contrast agents. Moreover, dendrimers can be successfully used as conjugates that deliver several substances simultaneously. The potential to develop dendrimers with multifunctional abilities has served as an impetus for the design of new molecular platforms for medical diagnostics and therapeutics.     

Polymeric micelles in diagnostic imaging

The results are presented describing the use of polymeric micelles for gamma, magnetic resonance (MR), and computed tomography (CT) imaging. Micelle-forming diacyllipid-PEG conjugates were loaded with monomeric and polymeric amphiphilic chelates, containing entrapped metals, such as 111-In or Gd, and used for the experimental gamma and MR imaging of lymphatics in rabbits. The method is described to prepare polymeric iodine-containing PEG-based micelles which may act as a long-circulating blood pool imaging agent for CT. Experimental CT-imaging performed in mice and rabbits demonstrated high potential of a micellar contrast agent.     

Polymeric Micelles in Cancer Immunotherapy

Cancer immunotherapies have generated some miracles in the clinic by orchestrating our immune system to combat cancer cells. However, the safety and efficacy concerns of the systemic delivery of these immunostimulatory agents has limited their application. Nanomedicine-based delivery strategies (e.g., liposomes, polymeric nanoparticles, silico, etc.) play an essential role in improving cancer immunotherapies, either by enhancing the anti-tumor immune response, or reducing their systemic adverse effects. The versatility of working with biocompatible polymers helps these polymeric nanoparticles stand out as a key carrier to improve bioavailability and achieve specific delivery at the site of action. This review provides a summary of the latest advancements in the use of polymeric micelles for cancer immunotherapy, including their application in delivering immunological checkpoint inhibitors, immunostimulatory molecules, engineered T cells, and cancer vaccines.     

A Fluorinated Detergent for Membrane‐Protein Applications

Surfactants carrying fluorocarbon chains hold great promise as gentle alternatives to conventional hydrocarbon‐based detergents for the solubilization and handling of integral membrane proteins. However, their inertness towards lipid bilayer membranes has limited the usefulness of fluorinated surfactants in situations where detergent‐like activity is required. We demonstrate that fluorination does not necessarily preclude detergency, as exemplified by a fluorinated octyl maltoside derivative termed F₆OM. This nonionic compound readily interacts with and completely solubilizes phospholipid vesicles in a manner reminiscent of conventional detergents without, however, compromising membrane order at subsolubilizing concentrations. Owing to this mild and unusual mode of detergency, F₆OM outperforms a lipophobic fluorinated surfactant in chaperoning the functional refolding of an integral membrane enzyme by promoting bilayer insertion in the absence of micelles.     

Suprasomes: an emerging platform for cancer theranostics

<正>Vesicular drug delivery systems(DDSs) are important in modern medicine, especially for cancer theranostics [1].Traditional vesicular DDSs, such as liposomes and polymersomes, have received a lot of attention owing to excellent delivery capabilities. However, due to the instability,     

载药磁性阳离子高聚物脂质体的制备及表征

通过羧甲基壳聚糖接枝二甲基十八烷基环氧丙基氯化铵, 合成了水油两溶性的羧甲基壳聚糖十八烷基季铵盐(QACMC), 并用其代替合成磷脂与胆固醇反应, 制备阳离子高聚物脂质体(CPL). 利用阳离子高聚物脂质体包覆水溶性Fe3O4磁流体, 构建磁性阳离子高聚物(MCPL)体系. 用TEM, DLS, VSM, FTIR及Zeta电位仪等对所制样品进行表征. 结果表明, 磁性阳离子高聚物脂质体在水相中可稳定存在, 粒径可达到15.3 nm, 分散性较好, Zeta电位可达到+38.22 mV, 比饱和磁化强度为27.9 A·m2/kg, 具有超顺磁性; MCPL对药物长春新碱的包封率可达到93.1%, 在Tris-HCl(pH=7.4)缓冲溶液中具有良好的缓控释功能.     

新型仿生聚合物胶束用于纳米药物载体的研究

对两亲性聚合物进行设计和优化, 从细胞膜仿生的设计出发, 利用原子转移自由基聚合, 制备了一种以胆固醇为疏水段、以仿细胞膜磷酸胆碱基聚合物为亲水段的两亲性分子CMPC. 在对其溶液胶束自组装行为进行探索的基础上, 以水包油(O/W)溶剂挥发法制备了包含抗癌药物阿霉素(ADR)的纳米抗癌药物载体, 通过体外细胞培养, 研究了仿细胞膜两亲分子的细胞相容性, 并对抗癌纳米药物载体抗肿瘤细胞的药效进行了初步研究.     

温度响应性单分子聚合物胶束

单分子聚合物胶束和传统的胶束一样具有核-壳结构,因其结构固定并具有良好的热力学稳定性而越来越受到研究者的关注。当这类胶束的核层或者壳层含有温敏性高分子的时候就可以形成具有温度响应性的单分子聚合物胶束。近年来,人们在温敏性的单分子聚合物胶束的合成与性能研究方面做了大量的工作。本文概述了具有温度响应行为的单分子聚合物胶束的类型、制备方法以及应用等方面取得的新进展,同时结合本实验室的工作,总结了基于超支化大分子的温敏性单分子聚合物胶束的相转变行为研究,并对这类胶束体系的发展进行了展望。