Cancer causes the second-highest rate of death world-wide. A major shortcoming inherent in most of anticancer drugs is their lack of tumor selectivity. Nanodrugs for cancer therapy administered intravenously escape renal clearance, are unable to penetrate through tight endothelial junctions of normal blood vessels and remain at a high level in plasma. Over time, the concentration of nanodrugs builds up in tumors due to the EPR effect, reaching several times higher than that of plasma due to the lack of lymphatic drainage. This review will address in detail the progress and prospects of tumor-targeting via EPR effect for cancer therapy.
Glioblastoma multiforme (GBM) is a highly aggressive form of brain cancer that is difficult to treat due to its resistance to both radiation and chemotherapy. This resistance is largely due to the unique biology of GBM cells, which can evade the effects of conventional treatments through mechanisms such as increased resistance to cell death and rapid regeneration of cancerous cells. Additionally, the blood–brain barrier makes it difficult for chemotherapy drugs to reach GBM cells, leading to reduced effectiveness. Despite these challenges, there are several treatment options available for GBM. The standard of care for newly diagnosed GBM patients involves surgical resection followed by concurrent chemoradiotherapy and adjuvant chemotherapy. Emerging treatments include immunotherapy, such as checkpoint inhibitors, and targeted therapies, such as bevacizumab, that attempt to attack specific vulnerabilities in GBM cells. Another promising approach is the use of tumor-treating fields, a type of electric field therapy that has been shown to slow the growth of GBM cells. Clinical trials are ongoing to evaluate the safety and efficacy of these and other innovative treatments for GBM, intending to improve with outcomes for patients.
Nano silver is one of the most widely used engineering nanomaterials with antimicrobial activity against bacteria, fungi, and viruses. However, the widespread application of nano silver preparations in daily life raises concerns about public health. Although several review articles have described the toxicity of nano silver to specific major organs, an updated comprehensive review that clearly and systematically outlines the harmful effects of nano silver is lacking. This review begins with the routes of exposure to nano silver and its distribution in vivo. The toxic reactions are then discussed on three levels, from the organ to the cellular and subcellular levels. This review also provides new insights on adjusting the toxicity of nano silver by changing their size and surface functionalization and their combination with other materials to form a composite formulation. Finally, future development, challenges, and research directions are discussed.
Targeted
delivery of chemotherapeutics to tumors has the potential
to reach a high dose at the tumor while minimizing systemic exposure.
Incorporation of antibody within a micellar platform represents a
drug delivery system for tumor-targeted delivery of antitumor agents.
Such modified immunomicelles can result in an increased accumulation
of antitumor agents and enhanced cytotoxicity toward cancer cells.
Here, mixed dendrimer micelles (MDM) composed of PEG2k-DOPE-conjugated
generation 4 polyamidoamine dendrimer G4-PAMAM-PEG2k-DOPE
and PEG5k-DOPE were coloaded with doxorubicin and siMDR-1.
This formulation was further modified with monoclonal antibodies 2C5
with nucleosome-restricted specificity that effectively recognized
cancer cells via the cell-surface-bound nucleosomes. Micelles with
attached 2C5 antibodies significantly enhanced cellular association
and tumor killing in both monolayer and spheroid tumor models as well
as in vivo in experimental animals compared to the
nontargeted formulations.
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