Nanomedicines as emerging platform for simultaneous delivery of cancer therapeutics: new developments in overcoming drug resistance and optimizing anticancer efficacy

Abstract

Development and formulation of an efficient and safe therapeutic regimen for cancer theranostics are dynamically challenging. The use of mono-therapeutic cancer regimen is generally restricted to optimal clinical applications, on account of drug resistance and cancer heterogeneity. Combinatorial treatments can employ multi-therapeutics for synergistic anticancer efficacy whilst reducing the potency of individual moieties and diminishing the incidence of associated adverse effects. The combo-delivery of nanotherapeutics can optimize anti-tumor efficacy while reversing the incidence of drug resistance, aiming to homogenize pharmacological profile of drugs, enhance circulatory time, permit targeted drug accumulation, achieve multi-target dynamic approach, optimize target-specific drug binding and ensure sustained drug release at the target site. Numerous nanomedicines/nanotherapeutics have been developed by having dynamic physicochemical, pharmaceutical and pharmacological implications. These innovative delivery approaches have displayed specialized treatment effects, alone or in combination with conventional anticancer approaches (photodynamic therapy, radiotherapy and gene therapy), while reversing drug resistance and potential off-target effects. The current review presents a comprehensive overview of nanocarrier aided multi-drug therapies alongside recent advancements, future prospects, and the pivotal requirements for interdisciplinary research.

Dual-targeted photothermal agents for enhanced cancer therapy

“…Indocyanine green (ICG), one of the cyanine dyes, has drawn a lot of attention due to its great biosafety, and has been approved by the Food and Drug Administration for clinical uorescence imaging. 112 ICG also shows great properties for tumor PTT, PDT and uorescence imaging, with satisfying water solubility and potential mitochondrial targeting, as well as splendid PCE properties. However, since ICG is easily cleared in vivo and has a short cycle time, it is usually administered via a delivery system.…”

Diabetic Cardiomyopathy: Current and Future Therapies. Beyond Glycemic Control

“…Moreover, in 2007 a meta-analysis showed a potentially increased risk of MI with the glucose lowering drug rosiglitazone, highlighting the necessity of thoroughly assessing the safety of this drug on the cardiovascular system ( Nissen and Wolski, 2007 ). For this reason, the Federal Drug Administration ( Hussain et al, 2018 ) and European Medicine Agency now require cardiovascular outcome trials for newly developed anti-hyperglycemic drugs in order to gain approval. This new regulation has resulted in a high number of cardiovascular outcome trials and increased the availability of important information on the effect of these drugs on cardiovascular health.…”

Revisiting the Diabetes-Heart Failure Connection

“…The optimal level of glycemic control in patients with HF is still uncertain, with some data suggesting that tight glycemic control increases the risk of hypoglycemia, which was associated with poorer outcomes [ 28 ]. Since the Federal Drug Administration (FDA) [ 29 ] and European Medicine Agency (EMA) began mandating cardiovascular outcome trials for newly developed antihyperglycemic drugs, many cardiovascular outcome trials have been conducted. The composite primary endpoint usually selected is major adverse cardiac events (MACE), which includes CV death, non-fatal MI, and non-fatal stroke.…”

“…The EMPA-REG-OUTCOME trial [ 95 •] reported significantly improved CV outcomes, including all-cause mortality, in patients who had received treatment with one specific anti-diabetic drug. This was the first trial to report positive CV outcomes since the European Medicines Agency (EMA) and Federal Drug Administration (FDA) [ 29 ] began requiring cardiovascular outcome trials for all new antihyperglycemic drugs. The EMPA-REG-OUTCOME trial was a randomized, double-blind, placebo-controlled trial with 7020 patients with T2DM and established cardiovascular disease.…”