Facile Preparation of Paclitaxel Nano-Suspensions to Treat Lung Cancer

Lung cancer is a worldwide issue which account for the death of thousands every year. Paclitaxel (PTX) as the first line chemotherapy drug to treat lung cancer, its clinical applications is largely limited by its poor solubility. The facile preparation of pharmaceutical formulations to increase the solubility as well as targetability of PTX is of vital importance in lung cancer treatment. Herein, we introduced a facile method to prepare PTX nano-suspensions (NSs), which have high drug loading as well as well-dispersed particle size. The in vitro cell experiments revealed its capability to enhance the drug accumulation in A549 cells than free PTX. Moreover, in vivo animal assay suggested its better tumor accumulation and antitumor efficacy than PTX injection (Taxol).

Biodistribution Study of Niosomes in Tumor-Implanted BALB/C Mice Using Scintigraphic Imaging

The purpose of this work was to study the biodistribution of niosomes in tumor-implanted BALB/c mice using gamma scintigraphy. Niosomes were first formulated and characterized, then radiolabeled with Technetium-99 m (99mTc). The biodistribution of 99mTc-labeled niosomes was evaluated in tumor-bearing mice through intravenous injection and imaged with gamma scintigraphy. The labeled complexes possessed high radiolabeling efficiency (98.08%) and were stable in vitro (>80% after 8 h). Scintigraphic imaging showed negligible accumulation in the stomach and thyroid, indicating minimal leaching of the radiolabel in vivo. Radioactivity was found mainly in the liver, spleen and kidneys. Tumor-to-muscle ratio indicated a higher specificity of the formulation for the tumor area. Overall, the formulated niosomes are stable both in vitro and in vivo, and show preferential tumor accumulation.

Cathepsin B-Overexpressed Tumor Cell Activatable Albumin-Binding Doxorubicin Prodrug for Cancer-Targeted Therapy

Prodrugs are bioreversible medications that should undergo an enzymatic or chemical transformation in the tumor microenvironment to release active drugs, which improve cancer selectivity to reduce toxicities of anticancer drugs. However, such approaches have been challenged by poor therapeutic efficacy attributed to a short half-life and low tumor targeting. Herein, we propose cathepsin B-overexpressed tumor cell activatable albumin-binding doxorubicin prodrug, Al-ProD, that consists of a albumin-binding maleimide group, cathepsin B-cleavable peptide (FRRG), and doxorubicin. The Al-ProD binds to in situ albumin, and albumin-bound Al-ProD indicates high tumor accumulation with prolonged half-life, and selctively releases doxorubicin in cathepsin B-overexpressed tumor cells, inducing a potent antitumor efficacy. Concurrently, toxicity of Al-ProD toward normal tissues with innately low cathepsin B expression is significantly reduced by maintaining an inactive state, thereby increasing the safety of chemotherapy. This study offers a promising approach for effective and safe chemotherapy, which may open new avenues for drug design and translational medicine.

Systematic Review of Cancer Targeting by Nanoparticles Revealed a Global Association between Accumulation in Tumors and Spleen

Active targeting of nanoparticles toward tumors is one of the most rapidly developing topics in nanomedicine. Typically, this strategy involves the addition of cancer-targeting biomolecules to nanoparticles, and studies on this topic have mainly focused on the localization of such formulations in tumors. Here, the analysis of the factors determining efficient nanoparticle targeting and therapy, various parameters such as types of targeting molecules, nanoparticle type, size, zeta potential, dose, and the circulation time are given. In addition, the important aspects such as how active targeting of nanoparticles alters biodistribution and how non-specific organ uptake influences tumor accumulation of the targeted nanoformulations are discussed. The analysis reveals that an increase in tumor accumulation of targeted nanoparticles is accompanied by a decrease in their uptake by the spleen. There is no association between targeting-induced changes of nanoparticle concentrations in tumors and other organs. The correlation between uptake in tumors and depletion in the spleen is significant for mice with intact immune systems in contrast to nude mice. Noticeably, modulation of splenic and tumor accumulation depends on the targeting molecules and nanoparticle type. The median survival increases with the targeting-induced nanoparticle accumulation in tumors; moreover, combinatorial targeting of nanoparticle drugs demonstrates higher treatment efficiencies. Results of the comprehensive analysis show optimal strategies to enhance the efficiency of actively targeted nanoparticle-based medicines.

Large-Scale Synthesis of Glutathione-Coated and 68Ga- Labeled Gold Nanoclusters for PET/CT Imaging of Tumors

Gold nanoclusters (AuNCs) have gained popular attention in recent years because of their efficient tumor accumulation through EPR effect and renal clearance. In this work, we put forward a new approach to prepare glutathione-coated, 68Ga-labeled AuNCs (68Ga-GHS@AuNCs) with ultrasmall sizes (< 2 nm) for PET/CT imaging of tumors. GHS@AuNCs has low cytotoxicity in vitro. PET/CT imaging revealed that the 68Ga-GHS@AuNCs could target tumor and be cleared by kidney efficiently. Our study demonstrates that 68Ga-GHS@AuNCs has great potential for detection of tumors.

Dye-loaded mesoporous polydopamine nanoparticles for multimodal tumor theranostics with enhanced immunogenic cell death

Background Tumor phototherapy especially photodynamic therapy (PDT) or photothermal therapy (PTT), has been considered as an attractive strategy to elicit significant immunogenic cell death (ICD) at an optimal tumor retention of PDT/PTT agents. Heptamethine cyanine dye (IR-780), a promising PDT/PTT agent, which can be used for near-infrared (NIR) fluorescence/photoacoustic (PA) imaging guided tumor phototherapy, however, the strong hydrophobicity, short circulation time, and potential toxicity in vivo hinder its biomedical applications. To address this challenge, we developed mesoporous polydopamine nanoparticles (MPDA) with excellent biocompatibility, PTT efficacy, and PA imaging ability, facilitating an efficient loading and protection of hydrophobic IR-780. Results The IR-780 loaded MPDA (IR-780@MPDA) exhibited high loading capacity of IR-780 (49.7 wt%), good physiological solubility and stability, and reduced toxicity. In vivo NIR fluorescence and PA imaging revealed high tumor accumulation of IR-780@MPDA. Furthermore, the combined PDT/PTT of IR-780@MPDA could induce ICD, triggered immunotherapeutic response to breast tumor by the activation of cytotoxic T cells, resulting in significant suppression of tumor growth in vivo. Conclusion This study demonstrated that the as-developed compact and biocompatible platform could induce combined PDT/PTT and accelerate immune activation via excellent tumor accumulation ability, offering multimodal tumor theranostics with negligible systemic toxicity. Graphical Abstract

Multifunctional Cyanine-Based Theranostic Probe for Cancer Imaging and Therapy

Cancer is one of the leading causes of death in the world. A cancer-targeted multifunctional probe labeled with the radionuclide has been developed to provide multi-modalities for NIR fluorescence and nuclear imaging (PET, SPECT), for photothermal therapy (PTT), and targeted radionuclide therapy of cancer. In this study, synthesis, characterization, in vitro, and in vivo biological evaluation of the cyanine-based probe (DOTA-NIR790) were demonstrated. The use of cyanine dyes for the selective accumulation of cancer cells were used to achieve the characteristics of tumor markers. Therefore, all kinds of organ tumors can be targeted for diagnosis and treatment. The DOTA-NIR790 labeled with lutetium-111 could detect original or metastatic tumors by using SPECT imaging and quantify tumor accumulation. The β-emission of 177Lu-DOTA-NIR790 can be used for targeted radionuclide therapy of tumors. The DOTA-NIR790 enabled imaging by NIR fluorescence and by nuclear imaging (SPECT) to monitor in real-time the tumor accumulation and the situation of cancer therapy, and to guide the surgery or the photothermal therapy of the tumor. The radionuclide-labeled heptamethine cyanine based probe (DOTA-NIR790) offers multifunctional modalities for imaging and therapies of cancer.

Applications of Pristine and Functionalized Carbon Nanotubes, Graphene, and Graphene Nanoribbons in Biomedicine

This review is dedicated to a comprehensive description of the latest achievements in the chemical functionalization routes and applications of carbon nanomaterials (CNMs), such as carbon nanotubes, graphene, and graphene nanoribbons. The review starts from the description of noncovalent and covalent exohedral modification approaches, as well as an endohedral functionalization method. After that, the methods to improve the functionalities of CNMs are highlighted. These methods include the functionalization for improving the hydrophilicity, biocompatibility, blood circulation time and tumor accumulation, and the cellular uptake and selectivity. The main part of this review includes the description of the applications of functionalized CNMs in bioimaging, drug delivery, and biosensors. Then, the toxicity studies of CNMs are highlighted. Finally, the further directions of the development of the field are presented.