The acceptance of nanoparticle technology in the quest for cancer treatment is due to its many potentials and possibilities of filling in the gaps in the limitations of the current treatment modalities. Insights into the possibilities of getting even more from this technology, as well as the synergistic properties of photothermal therapy (PTT) and photodynamic therapy (PDT)-the use of reactive oxygen species (ROS)-can also be exploited in the ablation of prostate cancer tumors. Therefore, the combination of gold and selenium photoactive nanoparticles as platforms for drug delivery via PTT/PDT in prostate cancer therapy, with a specific emphasis on the \'micro-carrier\' based approach, was discussed and explored in this review under relevant subtopics ranging from understanding the complex chemistry and biology of the pharmacologically active Se/Au-containing agents to giving a thorough knowledge of these therapeutic agents\' potential as a targeted and successful treatment strategy for prostate cancer by investigating the complex mechanisms behind their delivery, activation, and synergistic effects. Furthermore, this article presents a comprehensive overview of the current research environment, problems encountered, and future perspectives in the continuous war against prostate cancer.

Interest in the abscopal effect has been rekindled over the past decade with the advent of immunotherapy. Although purportedly elusive, this phenomenon is being increasingly reported. Venturing further using a multimodality approach with an array of systemic agents and unconventional modalities is direly needed. In this perspective, we describe the fundamentals of abscopal responses (ARs), explore combinations with systemic therapies that hold promise in eliciting ARs, and reconnoiter unconventional modalities that may induce ARs. Finally, we scrutinize prospective agents and modalities that exhibit preclinical ability to elicit ARs and discuss prognostic biomarkers, their limitations, and pathways of abscopal resistance for reproducibility.

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.

Nanotubular connections between mammalian cell types came into the focus only two decades ago, when \"live cell super-resolution imaging\" was introduced. Observations of these long-time overlooked structures led to understanding mechanisms of their growth/withdrawal and exploring some key genetic and signaling factors behind their formation. Unbelievable level of multiple supportive collaboration between tumor cells undergoing cytotoxic chemotherapy, cross-feeding\" between independent bacterial strains or \"cross-dressing\" collaboration of immune cells promoting cellular immune response, all via nanotubes, have been explored recently. Key factors and \"calling signals\" determining the spatial directionality of their growth and their overall in vivo significance, however, still remained debated. Interestingly, prokaryotes, including even ancient archaebacteria, also seem to use such NT connections for intercellular communication. Herein, we will give a brief overview of current knowledge of membrane nanotubes and depict a simple model about their possible \"historical role\".

Members of the 70 kDa stress protein family are found in nearly all subcellular compartments of nucleated cells where they fulfil a number of chaperoning functions. Heat shock protein 70 (HSP70), also termed HSPA1A, the major stress-inducible member of this family is overexpressed in a large variety of different tumour types. Apart from its intracellular localization, a tumour-selective HSP70 membrane expression has been determined. A membrane HSP70-positive tumour phenotype is associated with aggressiveness and therapy resistance, but also serves as a recognition structure for targeted therapies. Furthermore, membrane-bound and extracellularly residing HSP70 derived from tumour cells play pivotal roles in eliciting anti-tumour immune responses. Herein, we want to shed light on the multiplicity of different activities of HSP70, depending on its intracellular, membrane and extracellular localization with the goal to use membrane HSP70 as a target for novel therapies including nanoparticle-based approaches for the treatment of cancer.This article is part of the theme issue \'Heat shock proteins as modulators and therapeutic targets of chronic disease: an integrated perspective\'.

The benefit of nanomedicine in mitigating acute lung injury (ALI) is currently unknown. Therefore, we introduced the generation IV polyamidoamine dendrimers with neutral surface property (dendrimer) into our established ex vivo animal model and sought to determine their biodistribution to define their cellular uptake profile and to evaluate their potential as a drug delivery candidate for the treatment of ischemia-reperfusion-induced ALI.
Eight rabbit heart-lung blocks were harvested and exposed to 18 h of cold ischemia. The heart-lung blocks were then reperfused with rabbit donor blood. Dendrimer was conjugated to fluorescein isothiocyanate (D-FITC) for localization and quantification studies. D-FITC (30 mg or 150 mg) was injected into the bypass circuit and baseline, 1- and 2-h tissue samples were obtained to determine percent uptake. Low (10×) and high (40×) magnification images were obtained using confocal microscopy to confirm the accumulation and to determine the cellular targets of the dendrimer.
Four heart-lung blocks were exposed to 30 mg and four to 150 mg of D-FITC. After adjusting for dry weight, the mean uptake in the 30 and 150 mg samples after 2 h of reperfusion were 0.79 ± 0.16% and 0.39 ± 0.22% of perfused doses, respectively. Confocal imaging demonstrated dendrimer uptake in epithelial cells and macrophages.
Fluorescently tagged dendrimers demonstrated injury-dependent tissue accumulation in a variety of different cell types. This unique approach will allow conjugation to and delivery of multiple agents with the potential of mitigating ALI injury while avoiding systemic toxicity.

Nanoparticles, structures of less than 200 nm capable of delivering pharmacotherapeutics to sites of disease, have shown great promise for the treatment of many disease states. While no nanoparticle therapies for deep vein thrombosis are currently approved by the Food and Drug Administration, many of the unique features of these therapies have the potential to treat both deep vein thrombosis and its most significant sequela, postthrombotic syndrome, while limiting the hemorrhagic complications of current antithrombotic therapies. Nanoparticles are complex structures with several important variables that must be considered to engineer effective therapies. This article will review the structure and engineering of nanoparticles, as well as promising molecular targets for future investigation.

Adrenocortical carcinoma (ACC) has a poor prognosis with significant unmet clinical need due to late diagnosis, high rates of recurrence/metastasis and poor response to conventional treatment. Replacing tumor suppressor microRNAs (miRNAs) offer a novel therapy, however systemic delivery remains challenging. A number of miRNAs have been described to be under-expressed in ACC however it is not known if they form a part of ACC pathogenesis. Here we report that microRNA-7-5p (miR-7) reduces cell proliferation in vitro and induces G1 cell cycle arrest. Systemic miR-7 administration in a targeted, clinically safe delivery vesicle (EGFREDVTM nanocells) reduces ACC xenograft growth originating from both ACC cell lines and primary ACC cells. Mechanistically, miR-7 targets Raf-1 proto-oncogene serine/threonine kinase (RAF1) and mechanistic target of rapamycin (MTOR). Additionally, miR-7 therapy in vivo leads to inhibition of cyclin dependent kinase 1 (CDK1). In patient ACC samples, CDK1 is overexpressed and miR-7 expression inversely related. In summary, miR-7 inhibits multiple oncogenic pathways and reduces ACC growth when systemically delivered using EDVTM nanoparticles. This data is the first study in ACC investigating the possibility of miRNAs replacement as a novel therapy.