Cytotoxic chemotherapy or radiotherapy of cancer is limited by serious, sometimes life-threatening, side effects that arise from toxicities to sensitive normal cells because the therapies are not selective for malignant cells. So how can selectivity be improved? One strategy is to couple the therapeutics to antibodies or other ligands that recognize tumour-associated antigens. This increases the exposure of the malignant cells, and reduces the exposure of normal cells, to the ligand-targeted therapeutics.

Ligand-targeted therapeutics in anticancer therapy

Ribosome-inactivating proteins.

This review presents an overview about pharmaceutical and cosmetic topical products containing polymeric nanoparticles (nanospheres and nanocapsules), reporting the main preparation and characterization methods and the studies of penetration and transport of substances through the skin. The penetration and transport extent of those systems through the skin depends on the ingredients chemical composition, on the encapsulation mechanism influencing the drug release, on the size of nanoparticles and on the viscosity of the formulations. The polymeric nanoparticles are able to modify the activity of drugs, delay and control the drug release, and increase the drug adhesivity or its time of permanence in the skin. Briefly, the nanoparticles can be useful as reservoirs of lipophilic drugs to deliver them in the stratum corneum becoming an important strategy to control their permeation into the skin.

https://journals.sagepub.com/doi/pdf/10.1177/117739280700200002

Polymeric Nanoparticles, Nanospheres and Nanocapsules, for Cutaneous Applications

We have used RNA aptamer:gelonin conjugates to target and specifically destroy cells overexpressing the known cancer biomarker prostate-specific membrane antigen (PSMA) Aptamer:toxin conjugates have an IC50 of 27 nmol/L and display an increased potency of at least 600-fold relative to cells that do not express PSMA The aptamer not only promotes uptake into target cells but also decreases the toxicity of gelonin in non-target cells These results validate the notion that "escort aptamers" may be useful for the treatment of specific tumors expressing unique antigen targets

https://cancerres.aacrjournals.org/content/canres/66/12/5989.full.pdf

Aptamer:toxin conjugates that specifically target prostate tumor cells

The intracellular delivery of biofunctional enzymes or therapeutic proteins through systemic administration is of great importance in therapeutic intervention of various diseases. However, current strategies face substantial challenges owing to various biological barriers, including susceptibility to protein degradation and denaturation, poor cellular uptake, and low transduction efficiency into the cytosol. Here, we developed a biomimetic nanoparticle platform for systemic and intracellular delivery of proteins. Through a biocompatible strategy, guest proteins are caged in the matrix of metal–organic frameworks (MOFs) with high efficiency (up to ∼94%) and high loading content up to ∼50 times those achieved by surface conjunction, and the nanoparticles were further decorated with the extracellular vesicle (EV) membrane with an efficiency as high as ∼97%. In vitro and in vivo study manifests that the EV-like nanoparticles can not only protect proteins against protease digestion and evade the immune system ...

Self-Assembly of Extracellular Vesicle-like Metal–Organic Framework Nanoparticles for Protection and Intracellular Delivery of Biofunctional Proteins

Vascular endothelial growth factor (VEGF) plays a key role in the growth and metastasis of solid tumors. We generated a fusion protein containing VEGF121 linked by a flexible G4S tether to the toxin gelonin (rGel) and expressed this as a soluble protein in bacteria. Purified VEGF121/rGel migrated as an 84-kDa homodimer under nonreducing conditions. VEGF121/rGel bound to purified, immobilized Flk-1, and the binding was competed by VEGF121. Both VEGF121/rGel and VEGF121 stimulated cellular kinase insert domain receptor (KDR) phosphorylation. The VEGF121/rGel fusion construct was highly cytotoxic to endothelial cells overexpressing the KDR/Flk-1 receptor. The IC50 of the construct on dividing endothelial cells expressing 105 or more KDR/Flk-1 receptors per cell was 0.5–1 nM, as compared with 300 nM for rGel itself. Dividing endothelial cells overexpressing KDR were approximately 60-fold more sensitive to VEGF121/rGel than were nondividing cells. Endothelial cells overexpressing FLT-1 were not sensitive to the fusion protein. Human melanoma (A-375) or human prostate (PC-3) xenografts treated with the fusion construct demonstrated a reduction in tumor volume to 16% of untreated controls. The fusion construct localized selectively to PC-3 tumor vessels and caused thrombotic damage to tumor vessels with extravasation of red blood cells into the tumor bed. These studies demonstrate the successful use of VEGF121/rGel fusion construct for the targeted destruction of tumor vasculature in vivo.

https://www.pnas.org/content/pnas/99/12/7866.full.pdf

In vitro and in vivo studies of a VEGF121/rGelonin chimeric fusion toxin targeting the neovasculature of solid tumors.

Erratum: In vitro and in vivo studies of a VEGF121/rGelonin chimeric fusion toxin targeting the neovasculature of solid tumors (Proceedings of the National Academy of Sciences of the United States of America (June 11, 2002) 99:12 (7866-7871))

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In vitro and in vivo studies of a VEGF121/rGelonin chimeric fusion toxin targeting the neovasculature of solid tumors.

Erratum: In vitro and in vivo studies of a VEGF121/rGelonin chimeric fusion toxin targeting the neovasculature of solid tumors (Proceedings of the National Academy of Sciences of the United States of America (June 11, 2002) 99:12 (7866-7871))