Recent nanotechnology advancements to treat multidrug-resistance pancreatic cancer: Pre-clinical and clinical overview

Abstract

Pancreatic cancer (PC) remains one of the most lethal and incurable forms of cancer and has a poor prognosis. One of the significant therapeutic challenges in PC is multidrug resistance (MDR), a phenomenon in which cancer cells develop resistance toward administered therapy. Development of novel therapeutic platforms that could overcome MDR in PC is crucial for improving therapeutic outcomes. Nanotechnology is emerging as a promising tool to enhance drug efficacy and minimize off-target responses via passive and/or active targeting mechanisms. Over the past decade, tremendous efforts have been made to utilize nanocarriers capable of targeting PC cells while minimizing off-target effects. In this review article, we first give an overview of PC and the major molecular mechanisms of MDR, and then we discuss recent advancements in the development of nanocarriers used to overcome PC drug resistance. In doing so, we explore the developmental stages of this research in both pre-clinical and clinical settings. Lastly, we discuss current challenges and gaps in the literature as well as potential future directions in the field.

Drug Delivery Strategies for the Treatment of Pancreatic Cancer

“…In the design of nanoproducts, therapeutic agents can be conjugated to or encapsulated within the nanocarriers [ 36 ]. Nanoparticle-based drug delivery systems are designed to ensure effective and efficient delivery of cytotoxic agents to the tumor site at high concentrations compared with free drugs, improve the therapeutic agent’s pharmacokinetic profile factors such as solubility, half-life, and mean residence time, and minimize off-target exposure and toxicities [ 31 , 144 , 145 ]. Conversely, the high cost of production, burst release of the encapsulated drug, poor stability in the systemic circulation, off-target tissue accumulation, large molecular size, nanotoxicity, and batch-to-batch variation are some of the limitations associated with the use of nanovectors in drug delivery [ 144 ].…”

Responsive Nanomaterial Delivery Systems for Pancreatic Cancer Management

“…It is now accepted, as described in a recent extensive review, that pancreatic cancer is multifaceted, and that further understanding is needed of tumor genesis, progression, and the ongoing evolution of treatments, in order to develop better nanomedicine theranostic agents. [69] While existing review articles have broadly discussed the role of nanomedicines in managing pancreatic cancer or responsive nanomaterials in cancer generally, [70][71][72][73][74][75][76][77][78][79] there has been a notable absence of research specifically focused on stimuli-responsive materials tailored for pancreatic cancer. Consequently, our study addresses the specific realm of stimuli-responsive nanomaterials and explores the intricate mechanisms through which they are activated in pancreatic cancer.…”

One New Acid-Activated Hybrid Anticancer Peptide by Coupling with a Desirable pH-Sensitive Anionic Partner Peptide

“…In spite of tremendous progresses in cancer therapy, cancer remains a major public health problem worldwide, as the insufficient selectivity and multidrug resistance mostly produce adverse side effects and show resistance to almost available anticancer drugs. − Thus, it is more pressing to design and develop alternative anticancer agents with desirable therapeutic potential. Various targeting strategies have been applied to increase the therapeutic index of antitumor drugs by utilizing specific cell surface markers. , However, these targeting abilities have been compromised because of tumor heterogeneity. , It is known that the microenvironment around most tumors is more acidic compared with normal tissues due to the hypoxia and the abnormal tumor metabolic process. , The common acidic pH has been regarded as a desirable trigger to devise new pH-targeting strategies for tumor-specific therapy or drug delivery. − …”

“…In spite of tremendous progresses in cancer therapy, cancer remains a major public health problem worldwide, as the insufficient selectivity and multidrug resistance mostly produce adverse side effects and show resistance to almost available anticancer drugs. 1 − 3 Thus, it is more pressing to design and develop alternative anticancer agents with desirable therapeutic potential. Various targeting strategies have been applied to increase the therapeutic index of antitumor drugs by utilizing specific cell surface markers.…”