This review evaluates the literature on nanoparticle-based drug delivery systems for cancer treatment and assesses their efficacy. Nanoparticles have shown potential for improving anticancer agent delivery, reducing systemic toxicity, and enhancing therapeutic outcomes. Extensive studies have shown promising results in preclinical and clinical trials. However, challenges such as limited drug loading capacity, stability issues, and potential side effects need to be addressed to enhance clinical translation. Researchers are exploring strategies to improve drug loading capacity, such as modifying nanoparticle surfaces or developing novel drug encapsulation techniques. By increasing drug loading, the therapeutic efficacy of these systems can be significantly enhanced. Stability issues also pose a hurdle in clinical translation. To overcome stability issues, researchers are investigating methods to enhance the stability of nanoparticles, such as using protective coatings or optimising the formulation. Additionally, efforts are being made to minimise potential side effects by carefully selecting biocompatible materials for nanoparticle synthesis and conducting rigorous toxicity studies before moving forward with clinical trials. 

Review of the efficacy of nanoparticle-based drug delivery systems for cancer treatment

Autophagy is a mechanism involved in many human diseases and in cancers can have a cytotoxic/cytostatic or protective action, being in the latter case involved in multidrug resistance. Understanding which of these roles autophagy has in cancer is thus fundamental for therapeutical decisions because it permits to optimize the therapeutical approach by activating or inhibiting autophagy according to the progression of the disease. However, a serious drawback of cancer treatment is often the scarce availability of drugs and autophagy modulators at the sites of interest. In the recent years, several nanocarriers have been developed and investigated to improve the solubility, bioavailability, controlled release of therapeutics and increase their cytotoxic effect on cancer cell. Here we have reviewed only liposomes as carriers of chemotherapeutics and autophagy inhibitors because they are the sole nanoparticles that are actually used as drug carriers in oncological clinical settings. In this review after the analysis of the dual role of autophagy, of the main autophagic pathways, and of the role of autophagy in multidrug resistance, we will focus on the most effective liposomal formulations, thus highlighting the great potential of these targeting systems to defeat cancer diseases.

/pdf/the-exploitation-of-liposomes-in-the-inhibition-of-autophagy-4m5qki7sn5.pdf

The Exploitation of Liposomes in the Inhibition of Autophagy to Defeat Drug Resistance.

Despite profound advances in treatment approaches, gliomas remain associated with very poor prognoses. The residual cells after incomplete resection often migrate and proliferate giving a seed for highly resistant gliomas. The efficacy of chemotherapeutic drugs is often strongly limited by their poor selectivity and the blood brain barrier (BBB). Therefore, the development of therapeutic carrier systems for efficient transport across the BBB and selective delivery to tumor cells remains one of the most complex problems facing molecular medicine and nano-biotechnology. To address this challenge, a stimuli sensitive nanogel is synthesized using pre-polymer approach for the effective delivery of nano-irradiation. The nanogels are cross-linked via matrix metalloproteinase (MMP-2,9) substrate and armed with Auger electron emitting drug 5-[125 I]Iodo-4"-thio-2"-deoxyuridine ([125 I]ITdU) which after release can be incorporated into the DNA of tumor cells. Functionalization with diphtheria toxin receptor ligand allows nanogel transcytosis across the BBB at tumor site. Functionalized nanogels efficiently and increasingly explore transcytosis via BBB co-cultured with glioblastoma cells. The subsequent nanogel degradation correlates with up-regulated MMP2/9. Released [125 I]ITdU follows the thymidine salvage pathway ending in its incorporation into the DNA of tumor cells. With this concept, a highly efficient strategy for intracellular delivery of radiopharmaceuticals across the challenging BBB is presented.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/adhm.202100812

Protease Responsive Nanogels for Transcytosis across the Blood-Brain Barrier and Intracellular Delivery of Radiopharmaceuticals to Brain Tumor Cells.

Deciphering the relationship between caveolae-mediated intracellular transport and signalling events.

This paper is an overview of the recent advances in nanoporous anodic alumina sensing platforms based on the interaction of oligonucleotides and antibodies with bioelements (e.g., virus, bacteria, or biomarkers) that can cause or identify diseases. Nanoporous alumina is the common platform material for all these sensing devices that have an enormous potential for the next‐generation bioanalytical systems. Nanoporous alumina is a cost‐effective material with morphological flexibility that provides high sensitivity to the sensing systems due to its large surface‐to‐volume ratio. Immunosensors transduce the signal produced by the specific antibody–antigen interaction. They are widely used for clinical analysis due to the high selectivity and sensitivity of their immunoreaction, transduced by different methods (electrochemical, optical, piezoelectric, etc). Another important, outstanding and more recently type of biosensors are based on the oligonucleotic functionalization of nanoporous alumina. Oligonucleotides can bind to a wide variety of elements (small organic molecules, proteins, or cells) with high selectivity, specificity, and affinity, even higher to those of antibodies. The basic concepts and mechanisms of their sensing methods for health care biosensing are introduced. Their transduction methods and great potential applications will be evaluated and classified in detail, together with a discussion of possible future trends.

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/admt.202101591

Oligonucleotic Probes and Immunosensors Based on Nanoporous Anodic Alumina for Screening of Diseases

Last two decades have seen a tremendous and fascinating advancement in the field of drug development. Despite the progression in the scientific technology, the diseases of central nervous system (CNS) present a formidable challenge to the clinicians. Prospects to improve quality of life and halt or ameliorate age-related neurodegenerative diseases like Dementia, Alzheimer’s, Parkinson’s etc. are still far to measure. At present, around 1.5 billion people worldwide are suffering from one or another CNS disease [1]. As reviewed in 2017, around 47.5 million people around the globe are living with dementia. The prevalence of dementia is anticipated to be 75.63 million in 2030, reaching to 135.46 million by 2050, which is higher than original number estimated in the 2009 World Alzheimer report [2]. Specifically, in US about 5.2 million people are suffering from Alzheimer’s disease (AD), which has been cited as the sixth leading cause of death, and ranked fifth among those aged 65 years and older. Unless medical breakthroughs are made to favor the pharmacokinetics and pharmacodynamics of experimental therapeutics, it is estimated that by 2050, the number of AD patients may nearly triple from 5 million to a projected 14 million [3,4]. Of the all CNS related diseases, brain tumor is among the most challenging and lethal. Updated in January 2017, nearly 700,000 people in U.S. are living with CNS related tumor. It is estimated that nearly 80,000 cases of primary brain tumor would be diagnosed by the end of 2017. One third of the 32% of the diagnosed cases are anticipated to be malignant, and nearly 53,000 will be non-malignant. Sadly, by the end of 2017, nearly 17,000 people with CNS brain tumor will lose their battle with life [5]. Regardless of the scientific researches and technologies, no effective therapies are out in clinic for most of the brain tumors. The failure of vast majority of novel and current experiential therapeutics to reach/target the brain at a reasonable effective dose remains a major challenge. Despite great stride in understanding of the brain biology, from cellular to behavioral levels, the advances in basic science have not yet been fully developed in an interdisciplinary way, and a definitive translation from bench to bedside is still uncertain [6]. The scope of current communication focuses current challenges in brain-drug delivery, and significance of nanomedicine in crossing BBB, their downside and future prospects are also discussed.

/pdf/the-significance-of-nanomedicine-in-brain-targeted-drug-3j9mq5do97.pdf

The Significance of Nanomedicine in Brain-Targeted Drug Delivery: Crossing Blood-Brain Barriers

The aptamer is an oligonucleotide which is a short version of biological nucleic acids (such as DNA and RNA) with defined sequence of nucleotides. Based on the complexity of molecule, the aptamers lies in-between protein molecules and small chemical molecules. Aptamers have high specificity and affinity towards target proteins. They are screened from random sequences of oligonucleotides based on the highest affinity for target proteins using the SELEX (Systematic Evolution of Ligands by Exponential Enrichment). Researchers have discovered various applications of aptamers that are ready to replace the therapeutic use of biological proteins (such as antibodies) that have complexity in manufacturing and characterization. The present review describes the structural modification in aptamers such as PEGylation, substitution of functional groups, use of an enantiomeric oligonucleotide and its applications. Aptamers can be deactivated, when needed, by the use of reversal agent that contains oligonucleotide sequence complementary to aptamers. This property of aptamers makes them potential therapeutic from a safety point of view. In recent scenario, aptamers are developed for targeted drug delivery systems by conjugating with drug molecules or delivery vesicles such as liposomes. ‘Anti-sense Aptamers’ are being developed to silent the expression of genes responsible for the proliferative growth of tissue in cancer. Other applications of aptamers such as environmental monitoring and laboratory testing are also described in this review.

Aptamer: A Novel Therapeutic Oligonucleotide

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The Significance of Nanomedicine in Brain-Targeted Drug Delivery: Crossing Blood-Brain Barriers

Aptamer: A Novel Therapeutic Oligonucleotide