Current Cancer Drug Targets - Volume 16, Issue 6, 2016

Antibody-drug conjugates (ADCs) take the advantage of antigen specificity of monoclonal antibodies to deliver highly potent cytotoxic drugs selectively to antigen-expressing tumor cells. The recent approval of Adcetris™ and Kadcyla™ as well as emerging data from numerous ongoing clinical trials underscore the role of ADCs as a new therapeutic option for cancer patients. However, conventional conjugation methods generally result in a heterogeneous mixture of ADCs, which can result in significant therapeutic liabilities and can lead to complicated manufacturing processes. The increased understanding from the clinical investigation of current ADCs and site-specific bioconjugation technologies has enabled scientists to accelerate the discovery and development of the next generation ADCs with defined and homogeneous composition. The present manuscript reviews the recent advances and trends in the research and development of novel ADCs obtained by site-specific conjugation method.

Cisplatin is one of the leading chemotherapy drugs currently used in clinical settings. However, its serious side effects and its resistance developed by tumor cells hinder its usage. To decrease its side effects and maintain anti-cancer efficiency, various cisplatin based formulations were developed. In this minireview, we summarized the recent progress of cisplatin delivery strategies, including direct delivery, prodrug delivery and combination delivery. Key challenges preventing the development of improved drug formulations were identified, and effective approaches to address these issues were discussed in the context of these recent works.

Chemotherapeutic treatment of cancers is a challenging endeavor, hindered by poor selectivity towards tumorous tissues over healthy ones. Preferentially delivering a given drug to tumor sites necessitates the use of targeting elements, of which there are a wide range in development. In this Review, we highlight recent examples of peptide-based targeting ligands that have been exploited to selectively deliver a chemotherapeutic payload to specific tumor-associated sites such as the vasculature, lymphatics, or cell surface. The advantages and limitations of such approaches will be discussed with a view to potential future development. Additionally, we will also examine how peptide-based ligands can be used diagnostically in the detection and characterization of cancers through their incorporation into imaging agents.

Despite being one of the most effective broad-spectrum chemotherapeutic agents in the treatment of cancers, the clinical applications of bleomycins (BLMs) have been limited due to their poor drug delivery abilities, and the side effect of causing lung fibrosis. With the increased therapeutics and the reduction of side effects, research and development of targeted drug delivery systems (TDDS) with BLMs have become essential for the expansive clinical usage of BLM-based therapeutics. This review summarizes the recent developments of various TDDS for BLMs, including techniques such as photochemical internalization, ultrasound, and micelle, liposome, and nanoparticle formation. The advantages and disadvantages for each delivery approach are outlined, along with the specific challenges associated with each delivery system.

Cancer has become one of the leading causes of increased mortality. The currently employed diagnostic and therapeutic modality offers only minimal specificity towards cancerous cells and affects normal healthy cells. Targeted drug delivery systems have shown an improved efficiency in the diagnosis and treatment of various cancers, as the targeted molecules specifically reach the tumor cells without exerting any undesirable effects on the normal healthy cells. Recent findings have shown that disruption of blood vasculature and lymphatics is efficient in treating various cancers. As these vessels supply nutrient and oxygen, remove wastes and help in the metastasis; therapeutic agents targeting them will be highly useful. Of the various ligands used for targeting blood vasculature and lymphatics, peptides possess great advantage over other molecules. This review article is aimed at focusing the recent findings and developments on the peptides as targeting ligands for the improved anti-angiogenesis therapy.

The application of nanoparticles (NPs) offers new prospects for the early detection and effective therapy of colorectal cancer (CRC). Various NPs have been designed and explored as diagnostic and/or therapeutic drug delivery vehicles. To achieve selective treatment and to reduce toxicity, these nanoparticles are usually endowed with targeting abilities. Passive targeting is based on the extravasation and enhanced permeability and retention effect of tumors, while active targeting always involves binding to specific ligands that are recognizable by CRC tissues, such as vascular endothelial growth factor, folate, monoclonal antibodies (mAbs), aptamers, and membrane penetrating peptides. In addition, contrast agents, such as gadolinium complexes and iron oxide particles, can be introduced into the delivery system to enable MR imaging and lesion detection. Furthermore, smart carriers have been gradually applied to the delivery system. These carriers are designed to respond to certain changes in the bio-environment and release encapsulated contents on demand, thus achieving effective drug concentrations at tumor sites. This review focuses on recent advances of NP technology for the targeted diagnosis and treatment of CRC and aims to unveil the emerging possibilities of using nanocarriers to enhance therapeutic applications.

Objective: To investigate the feasibility of superparamagnetic iron oxide (SPIO) nanoparticles (SPIO) as a magnetic resonance (MR) contrast agent to enhance tumor imaging in vivo. Methods: Hydrophobic SPIO (oil-soluble SPIO; OSPIO) and hydrophilic SPIO (water-soluble SPIO; WSPIO) were loaded in methoxy-poly(ethylene glycol)-block-poly(D,L-lactic acid) (PEG-PDLLA) nanovesicles. Three groups of nude mice (n=12/group) xenografted with human colorectal carcinoma (LoVo) cells were injected into the caudal vein with WSPIO, OSPIO-loaded nanovesicles, or WSPIO-loaded nanovesicles. MRI scans were performed on all of the mice, and the relative T2 values were measured in the tumor and the liver. The differences in these T2 values between the three groups were compared. Results: The peak relative T2 values in the tumors detected by the OSPIO- or WSPIO-loaded contrast agents were reduced by 10.12% and 11.40%, respectively. The relative T2 values in the WSPIO- and OSPIO-loaded polymeric nanovesicle groups were more pronounced than the relative T2 value in the WSPIO group (P<0.05), but there was no significant difference in the T2 value between the OSPIO- and WSPIO-loaded vesicle groups (P#158;0.05). The greatest T2 value decreases in the liver in the WSPIO, OSPIO-loaded and WSPIO-loaded vesicle groups were 32.85%, 52.77% and 56.89%, respectively. The decrease in the T2 values was more pronounced in the WSPIO- and OSPIO-loaded nanovesicle groups than in the WSPIO group (P<0.05) and was more apparent in the WSPIO-loaded nanovesicle group than in the OSPIO-loaded nanovesicle group (P<0.05). Conclusion: SPIO-loaded polymeric nanovesicles generate significant T2WI signal intensity decreases in vivo and are anticipated to be used as novel and effective contrast agents for tumor imaging.