Nanoparticle-Mediated Combination Therapy: Two-in-One Approach for Cancer

Abstract

Cancer represents a group of heterogeneous diseases characterized by uncontrolled growth and spread of abnormal cells, ultimately leading to death. Nanomedicine plays a significant role in the development of nanodrugs, nanodevices, drug delivery systems and nanocarriers. Some of the major issues in the treatment of cancer are multidrug resistance (MDR), narrow therapeutic window and undesired side effects of available anticancer drugs and the limitations of anticancer drugs. Several nanosystems being utilized for detection, diagnosis and treatment such as theranostic carriers, liposomes, carbon nanotubes, quantum dots, polymeric micelles, dendrimers and metallic nanoparticles. However, nonbiodegradable nanoparticles causes high tissue accumulation and leads to toxicity. MDR is considered a major impediment to cancer treatment due to metastatic tumors that develop resistance to chemotherapy. MDR contributes to the failure of chemotherapies in various cancers, including breast, ovarian, lung, gastrointestinal and hematological malignancies. Moreover, the therapeutic efficiency of anticancer drugs or nanoparticles (NPs) used alone is less than that of the combination of NPs and anticancer drugs. Combination therapy has long been adopted as the standard first-line treatment of several malignancies to improve the clinical outcome. Combination therapy with anticancer drugs has been shown to generally induce synergistic drug actions and deter the onset of drug resistance. Therefore, this review is designed to report and analyze the recent progress made to address combination therapy using NPs and anticancer drugs. We first provide a comprehensive overview of the angiogenesis and of the different types of NPs currently used in treatments of cancer; those emphasized in this review are liposomes, polymeric NPs, polymeric micelles (PMs), dendrimers, carbon NPs, nanodiamond (ND), fullerenes, carbon nanotubes (CNTs), graphene oxide (GO), GO nanocomposites and metallic NPs used for combination therapy with various anticancer agents. Nanotechnology has provided the convenient tools for combination therapy. However, for clinical translation, we need continued improvements in the field of nanotechnology.

Antitumor Features of Vegetal Protein-Based Nanotherapeutics

“…A specific approach for contrasting the drug resistance of tumors is the employment of a combination of two active compounds aiming at different targets in order to obtain a synergistic anticancer effect [118]. The use of biocompatible delivery systems able to retain two or more drugs in the same structure has been investigated over the last decade in order to exploit this feature and various formulations have been developed [119][120][121][122][123][124].…”

The Effect of Nanosystems on ATP-Binding Cassette Transporters: Understanding the Influence of Nanosystems on Multidrug Resistance Protein-1 and P-glycoprotein

“…Many of these variables should be considered in the adoption of the best chemotherapy for patients [1]. Unfortunately, the efficiency of treatment regimens to a wide range of neoplasms can highly vary and many authors argue that changes in the development of new treatments should be considered [4,5].…”

“…This rationale can be achieved by using molecules and/or monoclonal antibodies that will interact directly with the transporters extracellularly or act as an antagonist in the cytoplasm [14]. Another strategy is to use interference RNA (RNAi) to silence the expression of ABC genes [5].…”

“…Nanoparticles can be put together to create highly customized nanosystems with a diverse set of features that can help raise specificity to neoplastic cells and safeness to the treatment, along with other advantages such as better solubility and stability. The key design is to turn nanoparticles into complex functionalized carriers of anti-cancer agents, tumor microenvironmental modulators and targeting molecules, delivering them to tumor sites in a highly specific fashion [5]. In fact, a few approved nanomedicines are already available such as Doxil ® and Caelyx ® which are liposomal nanoparticle formulation that increase the bioavailability of doxorubicin (DOX) to tumor cells, and that can be further functionalized using nanotechnology to overcome other limitations [43].…”

Electron correlation effects in isomers of C20

“…It is also an exceptional radical scavenger, is highly robust, and can be easily modified, allowing for the formation of derivatives with varying physical characteristics [10]. These properties make the fullerenes valuable for biological applications, and they have indeed demonstrated antioxidant, antiviral, and anticancerous activity [4,[11][12][13][14]. Fullerenes also behave as strong electron-acceptors within energy conversion systems, and thus C 60 derivatives have been studied extensively as components of organic solar cells [15].…”