Current Topics in Medicinal Chemistry - Volume 17, Issue 16, 2017

Inorganic nanoparticles, which can absorb and convert near infrared (NIR) light to heat to ablate cancer cells, have been widely investigated in photothermal therapy. However, the inherent poor solubility and acute systemic toxicity of these inorganic particles hinder their application in clinical practice. Polymeric nanocomposites materials containing both inorganic nanoparticles and polymers could be harnessed to achieve enhanced photothermal therapeutic effect as well as improved biocompatibility and multi-responsiveness. Synergistic chemo-photothermal efficacy towards cancer cells and tumor tissue can thus be realized through such multi-functional and multi-responsive polymeric nanocomposites. In this review, the recent developments in polymeric nanocomposites based on different types of inorganic nanoparticles (i.e. gold, carbon nanotube, graphene, and upconversion nanoparticles) for NIR-triggered cancer therapy are summarized.

Theranostic medicine has become more promising in cancer treatment, where the cancer diagnosis and chemotherapy are combined for early diagnosis and precise treatment with improved efficacy and reduced side effects. Nanotechnology has played a critical role in developing various nanomaterials with engendered smart functions and targeted delivery. The rapid development of structural DNA nanotechnology has enabled the design and fabrication of complex nanostructures with prescribed 1D, 2D and 3D patterns in vitro and in vivo. Self-assembled DNA nanostructures can serve as drug delivery platforms that are integrated with various functions ranging from molecular recognition and computations, dynamically structural switch to carrying molecular payloads and selectively release. In this review, we summarize recent exciting progress of using DNA nanostructures to engineer novel smart drug-delivery systems potential for treating cancer.

DNA can be self-assembled into programmable two-dimensional and three-dimensional nanoarchitectures with arbitrarily predetermined sizes and shapes. Because of the addressable arbitrary size and shape, great capacity of cargo loading, ability to be internalized by cells, the stability of structures under physiological conditions and excellent biocompatibility, the pristine DNA nanostructures are explored as drug vehicles in drug delivery. In addition, DNA block copolymer and DNADendron hybrid, as new building blocks, can be self-assembled into different kinds of ordered structures, e.g., nanofibers, spherical micelles, and vesicles, in aqueous solution. Recent studies have shown that some of these nanostructures could easily enter cells with excellent cell uptake efficiency. Herein, this review will mainly introduce the self-assembly behavior of pristine DNA and DNA hybrid materials including DNA block copolymers and DNA-Dendron hybrids, and their application in drug delivery.

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that are preferentially expanded in cancer. They arise from myeloid progenitor cells that do not differentiate into mature dendritic cells (DCs), granulocytes, or macrophages, and are rather thought to play a pivotal role in immune escape and cancer progression. MDSCs are characterized by the ability to suppress T cell proliferation and cytotoxicity, inhibit natural killer T (NKT) cell activation, and induce the differentiation and expansion of regulatory T cells (Treg). MDSC levels have been shown to correlate negatively with prognosis and overall survival of patients with cancers of various types and stages. The role of MDSCs in cancer progression represents a promising target for effective cancer immunotherapy. In this review, we discuss the mechanisms of MDSC functions, their influence on tumor progression and metastasis, and finally focus on up to date nanoparticle approaches that target and antagonize MDSCs in tumor-bearing hosts. The development of multifunctional nanoparticle systems for effective imaging, assessment and manipulation of MDSCs will represent strategic theranostic innovations that may improve cancer staging, therapeutic outcomes, and overall patient survival.

With the progress of nanotechnology, the treatment of cancer by photothermal therapy (PTT) and photodynamic therapy (PDT) using theranostic nanomaterials based on iron oxide (Fe3O4) and gold (Au) nanoparticles (NPs) has received much attention in recent years. The Fe3O4 NPs have been used as imaging-guided PTT of cancer due to their high relaxivity, excellent contrast enhancement, and less toxicity. The Au NPs have been widely employed as a contrast agent for CT imaging of different biological systems due to their enhanced X-ray attenuation property. Due to the strong surface plasmon resonance (SPR) absorption intensity in near-infrared (NIR) region, Au NPs have been considered for imaging-guided PTT of cancer. Since the photosensitizer, which plays an important role in PDT of cancer, can be efficiently conjugated with Fe3O4 and Au NPs, these NPs have also been considered for imaging-guided PDT of cancer. It has been found that both Fe3O4 and Au NPs allow passive targeting of tumors through enhanced permeability and retention (EPR) effect to improve the treatment efficacy in PTT and PDT. The present review focuses on the recent developments of Fe3O4 and Au-based NPs as theranostics for imaging-guided PTT and PDT of cancer.

The interaction between cancer cells and their microenvironment is an indispensable link in cancer progression that occurs on the interfaces between them and presents typical biointerfacial behavior. Recently, the cancer cell/microenvironment interface has begun to attract more attention because of its fundamental roles in cancer growth and metastasis, which is promising for the efficacy of anti-cancer drugs and other important effects. In this review, we focused on mechanical coupling of the biointerfaces and their application in cancer early diagnosis, the pharmacology of anticancer agents and the design of the anticancer drug carriers. Newly developed strategies for cancer therapy based on mechanical coupling, such as correcting cell mechanics defects, tunable rigidity for drug delivery and topography-coupled-mechanical drug design, and drug screening, provide a proof of concept that cell mechanics offer a rich drug target space, allowing for the possible corrective modulation of tumor cell behavior. Biomechanopharmacology is therefore important to recognize the biomechanical factors and to control them not only for improvement in our knowledge of cancer but also for the development of new drugs and new uses of old drugs.