The unique structure and physiology of a tumor microenvironment impede intra-tumoral penetration of chemotherapeutic agents. A novel iRGD peptide that exploits the tumor microenvironment can activate integrin-dependent binding to tumor vasculatures and neuropilin-1 (NRP-1)-dependent transport to tumor tissues. Recent studies have focused on its dual-targeting ability to achieve enhanced penetration of chemotherapeutics for the efficient eradication of cancer cells. Both the covalent conjugation and the co-administration of iRGD with chemotherapeutic agents and engineered delivery vehicles have been explored. Interestingly, the iRGD-mediated drug delivery also enhances penetration through the blood–brain barrier (BBB). Recent studies have shown its synergistic effect with BBB disruptive techniques. The efficacy of immunotherapy involving immune checkpoint blockades has also been amplified by using iRGD as a targeting moiety. In this review, we presented the recent advances in iRGD technology, focusing on cancer treatment modalities, including the current clinical trials using iRGD. The iRGD-mediated nano-carrier system could serve as a promising strategy in drug delivery to the deeper tumor regions, and be combined with various therapeutic interventions due to its novel targeting ability.

Alzheimer’s disease (AD) is an irreversible and progressive neurodegenerative disorder. Most existing treatments only provide symptomatic solutions. Here, we introduce currently available commercial drugs and new therapeutics, including repositioned drugs, to treat AD. Despite tremendous efforts, treatments targeting the hallmarks of AD show limited efficacy. Challenges in treating AD are partly caused by difficulties in penetrating the blood–brain barrier (BBB). Recently, nanoparticle (NP)-based systems have shown promising potential as precision medicines that can effectively penetrate the BBB and enhance the targeting ability of numerous drugs. Here, we describe how NPs enter the brain by crossing, avoiding, or disrupting the BBB. In addition, we provide an overview of the action of NPs in the microenvironment of the brain for the treatment of AD. Diverse systems, including liposomes, micelles, polymeric NPs, solid-lipid NPs, and inorganic NPs, have been investigated for NP drug loading to relieve AD symptoms, target AD hallmarks, and target moieties to diagnose AD. We also highlight NP-based immunotherapy, which has recently gained special attention as a potential treatment option to disrupt AD progression. Overall, this review focuses on recently investigated NP systems that represent innovative strategies to understand AD pathogenesis and suggests treatment and diagnostic modalities to cure AD.

Atomic force microscopy (AFM) is a promising method for generating high-spatial-resolution images, providing insightful perspectives on the nanomechanical attributes of soft matter, including cells, bacteria, viruses, proteins, and nanoparticles. AFM is widely used in biological and pharmaceutical sciences because it can scrutinize mechanical properties under physiological conditions. We comprehensively reviewed experimental techniques and fundamental mathematical models to investigate the mechanical properties, including elastic moduli and binding forces, of soft materials.

Parkinson’s disease is a neurodegenerative disorder characterized by cardinal motor symptoms resulting from the loss of dopaminergic neurons in the substantia nigra pars compacta. Although current medications may alleviate its symptoms, Parkinson’s disease remains incurable. Astaxanthin is an antioxidant and anti-inflammatory agent; however, its high susceptibility to oxidative degradation and low aqueous solubility limit its therapeutic efficacy. This study aimed to improve the pharmaceutical properties and neuroprotective effects of astaxanthin for Parkinson’s disease treatment by using lactoferrin-conjugated astaxanthin-loaded liposomes (Lf-ASX-LPs). We successfully formulated Lf-ASX-LPs with high encapsulation efficiency (97.6%) and favorable physical characteristics (diameter: 109.8 ± 1.1 nm; polydispersity index: 0.18 ± 0.01; zeta potential: − 9.5 ± 1.1 mV). Lf-functionalized liposomes demonstrated enhanced cellular uptake and permeation in a Transwell^® study, showing a 16.7-fold higher internalization in SH-SY5Y cells over 24 h than those without Lf conjugation. Additionally, Lf functionalization enhanced brain penetration ability, as demonstrated by a biodistribution study using nude mice, compared to LPs without Lf conjugation. In vitro, Lf-ASX-LPs reduced cell loss by 20.1% and oxygen species by 30.0%, ameliorated the reduction in mitochondrial membrane potential under 1-methyl-4-phenylpyridinium-induced toxicity by 40.1%, and reduced extracellular nitric oxide levels under lipopolysaccharide-induced toxicity by 32.0%, indicating cytoprotective and antioxidant effects. In a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson’s disease mouse model, treatment with Lf-ASX-LPs resulted in 5.0-, 3.1-, and 5.6-fold increases in dopamine levels, TH⁺ fiber density, and TH⁺ neurons, respectively, restoring dopaminergic neuron damage. The developed formulation also alleviated behavioral impairment and neuroinflammation, reducing astrocyte and microglial activation in the striatum and substantia nigra of the MPTP-treated animals. Thus, our formulation of Lf-ASX-LPs represents a promising strategy for providing neuroprotection and retarding Parkinson’s disease progression. Graphical abstract

Soyeun Park. J Cancer Prev 2016;21:73-80. http://dx.doi.org/10.15430/JCP.2016.21.2.73