Chitosan-Based Nano Systems for Natural Antioxidants in Breast Cancer Therapy.

Breast cancer is a major cause of death globally, accounting for around 13% of all deaths. Chemotherapy, the common treatment for cancer, can have side effects that lead to the production of reactive oxygen species (ROS) and an increase in oxidative stress in the body. Antioxidants are important for maintaining the health of cells and helping the immune system function properly. They play a crucial role in balancing the body's internal environment. Using natural antioxidants is an alternative to mitigate the harmful effects of oxidative stress. However, around 80% of natural antioxidants have limited effectiveness when taken orally because they do not dissolve well in water or other solvents. This poor solubility affects their ability to be absorbed by the body and limits their bioavailability. One strategy that has been considered is to increase their water solubility to increase their oral bioavailability. Chitosan-based nanoparticle (CSNP) systems have been extensively explored due to their reliability and simpler synthesis routes. This review focuses on the various methods of chitosan-based nanoformulation for developing effective oral dosage forms for natural antioxidants based on the pharmacokinetics and pharmacodynamics properties. Chitosan (CS) could be a model, because of its wide use in polymeric NPs research, thus providing a better understanding of the role of vehicles that carry natural antioxidants in maintaining the stability and enhancing the performance of cancer drugs.

Development and characterization of pH-responsive nanocarriers for chemo-photothermal combination therapy of acidic tumors.

The combination of photothermal therapy and chemotherapy has been considered a promising strategy for improving the excellent antitumor activities of these treatments. In this study, we developed a new simple type of pH-sensitive chemo-photothermal combination agent capable of repeated exposures to a near-infrared (NIR) laser and evaluated its anticancer efficacy in vitro and in vivo. Doxorubicin (Dox) and gold nanoclusters (GNCs) were successfully co-loaded into pH-sensitive nanoparticles (poly(ethylene glycol)-poly[(benzyl-l-aspartate)-co-(N-(3-aminopropyl)imidazole-L-aspartamide)] (PEG-PABI)), resulting in a particle size of approximately120 nm with a narrow size distribution. The dual drug-loaded nanoparticles (Dox/GNC-loaded PEG-PABI micelles (Dox/GNC-Ms)) showed consistent pH-sensitive properties and heat generation efficiency after repeated NIR laser exposure. In particular, GNC-M has improved photothermal stability while maintaining high photothermal conversion efficiency, addressing the shortcomings of previous gold nanoparticles. As the concentration of GNC-Ms, irradiation light exposure time, and light source intensity increased, the amount of heat generated and the anticancer effect increased. When Dox was encapsulated with GNCs (Dox/GNC-Ms), a faster drug release rate under acidic pH conditions and a strong synergistic effect against U87MG cells were observed. When the Dox/GNC-M system was extended to in vivo studies, it effectively increased the temperature of the tumor tissue under near-infrared irradiation and showed excellent anticancer efficacy. Therefore, the Dox/GNC-M system could be a simple but promising strategy for chemo-photothermal combination treatment capable of targeting acidic tumors.

Tumor microenvironment stimuli-responsive lipid-drug conjugates for cancer treatment.

Lipid drug conjugates (LDCs) have attracted considerable attention in the fields of drug delivery and pharmacology due to their ability to target specific cells, increase drug solubility, reduce toxicity, and improve therapeutic efficacy. These unique features make LDCs promising candidates for the treatment cancer, inflammation, and infectious diseases. In fact, by choosing specific linkers between the lipid and drug molecules, stimuli-responsive LDCs can be designed to target cancer cells based on the unique properties of the tumor microenvironment. Despite the fact that many reviews have described LDCs, few articles have focused on tumor microenvironmental stimuli-responsive LDCs for cancer treatment. Therefore, the key elements of these types of LDCs in cancer treatment will be outlined and discussed in this paper. Our paper goes into detail on the concepts and benefits of LDCs, the various types of tumor microenvironment stimuli-responsive LDCs (such as pH, redox, enzyme, or reactive oxygen species-responsive LDCs), and the current status of LDCs in clinical trials.

Effects of PEG-Linker Chain Length of Folate-Linked Liposomal Formulations on Targeting Ability and Antitumor Activity of Encapsulated Drug.

Introduction: Ligand-conjugated liposomes are promising for the treatment of specific receptor-overexpressing cancers. However, previous studies have shown inconsistent results because of the varying properties of the ligand, presence of a polyethylene glycol (PEG) coating on the liposome, length of the linker, and density of the ligand. Methods: Here, we prepared PEGylated liposomes using PEG-linkers of various lengths conjugated with folate and evaluated the effect of the PEG-linker length on the nanoparticle distribution and pharmacological efficacy of the encapsulated drug both in vitro and in vivo. Results: When folate was conjugated to the liposome surface, the cellular uptake efficiency in folate receptor overexpressed KB cells dramatically increased compared to that of the normal liposome. However, when comparing the effect of the PEG-linker length in vitro, no significant difference between the formulations was observed. In contrast, the level of tumor accumulation of particles in vivo significantly increased when the length of the PEG-linker was increased. The tumor size was reduced by >40% in the Dox/FL-10K-treated group compared to that in the Dox/FL-2K- or 5K-treated groups. Discussion: Our study suggests that as the length of PEG-linker increases, the tumor-targeting ability can be enhanced under in vivo conditions, which can lead to an increase in the antitumor activity of the encapsulated drug.

Development of AE147 Peptide-Conjugated Nanocarriers for Targeting uPAR-Overexpressing Cancer Cells.

PURPOSE: An AE147 peptide-conjugated nanocarrier based on PEGylated liposomes was developed in order to target the metastatic tumors overexpressing urokinase-type plasminogen activator receptor (uPAR), which cancer progression via uPA signaling. Therefore, the AE147 peptide-conjugated nanocarrier system may hold the potential for active targeting of metastatic tumors. METHODS: The AE147 peptide, an antagonist of uPAR, was conjugated to the PEGylated liposomes for targeting metastatic tumors overexpressing uPAR. Docetaxel (DTX), an anticancer drug, was incorporated into the nanocarriers. The structure of the AE147-conjugated nanocarrier, its physicochemical properties, and in vivo biodistribution were evaluated. RESULTS: The DTX-loaded nanocarrier showed a spherical structure, a high drug-loading capacity, and a high colloidal stability. Drug carrying AE147 conjugates were actively taken up by the uPAR-overexpressing MDA-MB-231 cancer cells. In vivo animal imaging confirmed that the AE147-conjugated nanoparticles effectively accumulated at the sites of tumor metastasis. CONCLUSION: The AE147-nanocarrier showed potential for targeting metastatic tumor cells overexpressing uPAR and as a nanomedicine platform for theragnosis applications. These results suggest that this novel nano-platform will facilitate further advancements in cancer therapy.

Recent Advances in pH- or/and Photo-Responsive Nanovehicles.

The combination of nanotechnology and chemotherapy has resulted in more effective drug design via the development of nanomaterial-based drug delivery systems (DDSs) for tumor targeting. Stimulus-responsive DDSs in response to internal or external signals can offer precisely controlled delivery of preloaded therapeutics. Among the various DDSs, the photo-triggered system improves the efficacy and safety of treatment through spatiotemporal manipulation of light. Additionally, pH-induced delivery is one of the most widely studied strategies for targeting the acidic micro-environment of solid tumors. Accordingly, in this review, we discuss representative strategies for designing DDSs using light as an exogenous signal or pH as an endogenous trigger.

Photo-Based Nanomedicines Using Polymeric Systems in the Field of Cancer Imaging and Therapy.

The use of photo-based nanomedicine in imaging and therapy has grown rapidly. The property of light in converting its energy into different forms has been exploited in the fields of optical imaging (OI) and phototherapy (PT) for diagnostic and therapeutic applications. The development of nanotechnology offers numerous advantages to overcome the challenges of OI and PT. Accordingly, in this review, we shed light on common photosensitive agents (PSAs) used in OI and PT; these include fluorescent and bioluminescent PSAs for OI or PT agents for photodynamic therapy (PDT) and photothermal therapy (PTT). We also describe photo-based nanotechnology systems that can be used in photo-based diagnostics and therapies by using various polymeric systems.