Targeted Delivery to Tumors: Multidirectional Strategies to Improve Treatment Efficiency

Malignant tumors are characterized by structural and molecular peculiarities providing a possibility to directionally deliver antitumor drugs with minimal impact on healthy tissues and reduced side effects. Newly formed blood vessels in malignant lesions exhibit chaotic growth, disordered structure, irregular shape and diameter, protrusions, and blind ends, resulting in immature vasculature; the newly formed lymphatic vessels also have aberrant structure. Structural features of the tumor vasculature determine relatively easy penetration of large molecules as well as nanometer-sized particles through a blood–tissue barrier and their accumulation in a tumor tissue. Also, malignant cells have altered molecular profile due to significant changes in tumor cell metabolism at every level from the genome to metabolome. Recently, the tumor interaction with cells of immune system becomes the focus of particular attention, that among others findings resulted in extensive study of cells with preferential tropism to tumor. In this review we summarize the information on the diversity of currently existing approaches to targeted drug delivery to tumor, including (i) passive targeting based on the specific features of tumor vasculature, (ii) active targeting which implies a specific binding of the antitumor agent with its molecular target, and (iii) cell-mediated tumor targeting

Synergistic Effect of the Combination of the Recombinant Toxin DARPin-LoPE and PDT against HER2-Positive Breast Cancer In Vitro

A promising strategy to enhance the therapeutic effectiveness for the treatment of oncological diseases involves the development of combined therapeutic schemes. In our work, we showed the therapeutic potential of the combined action of the anticancer targeted toxin and PDT against HER2-positive breast cancer in vitro. Photodynamic treatment led to photoinduced cell death with IC50 0.64 µM, and after incubation with the toxin for 48 h, IC50 was 2.8 pM. When using two therapeutic agents at IC50 doses, significant increases in the effectiveness were observed; the viability of the combination-treated cell culture did not exceed 10%. The calculated combination index was 0.07, indicating a significant synergistic effect caused by the agents

Far-red fluorescent murine glioma model for accurate assessment of brain tumor progression

Simple Summary The creation of stable fluorescent glioma cell lines opens prospects for the detailed characterization of the molecular mechanisms of glioma origin and pathogenesis, and the development of breakthrough therapeutic approaches to achieve maximum glioma destruction and minimize the risk of future metastases. Herein, we generated and characterized a novel fluorescent glioma GL261-kat cell line stably expressing a far-red fluorescent protein, TurboFP635 (Katushka). Using the orthotopic mouse glioma model and epi-fluorescence imaging, we demonstrate the detection of fluorescent glioma GL261-kat cells in mice, and observe an increase in the fluorescence signal during glioma progression, which is accompanied by a gradual development of neurological deficit and behavioral alterations in mice. We show that GL261-kat cells can be a useful tool for studying glioma biology, because they can accurately and non-invasively monitor the characteristics of glioma growth in brain tissue in orthotopic mouse models. Glioma is the most common brain tumor, for which no significant improvement in life expectancy and quality of life is yet possible. The creation of stable fluorescent glioma cell lines is a promising tool for in-depth studies of the molecular mechanisms of glioma initialization and pathogenesis, as well as for the development of new anti-cancer strategies. Herein, a new fluorescent glioma GL261-kat cell line stably expressing a far-red fluorescent protein (TurboFP635; Katushka) was generated and characterized, and then validated in a mouse orthotopic glioma model. By using epi-fluorescence imaging, we detect the fluorescent glioma GL261-kat cells in mice starting from day 14 after the inoculation of glioma cells, and the fluorescence signal intensity increases as the glioma progresses. Tumor growth is confirmed by magnetic resonance imaging and histology. A gradual development of neurological deficit and behavioral alterations in mice is observed during glioma progression. In conclusion, our results demonstrate the significance and feasibility of using the novel glioma GL261-kat cell line as a model of glioma biology, which can be used to study the initialization of glioma and monitor its growth by lifetime non-invasive tracking of glioma cells, with the prospect of monitoring the response to anti-cancer therapy

Controlled Formation of a Protein Corona Composed of Denatured BSA on Upconversion Nanoparticles Improves Their Colloidal Stability

In the natural fluidic environment of a biological system, nanoparticles swiftly adsorb plasma proteins on their surface forming a “protein corona”, which profoundly and often adversely affects their residence in the systemic circulation in vivo and their interaction with cells in vitro. It has been recognized that preformation of a protein corona under controlled conditions ameliorates the protein corona effects, including colloidal stability in serum solutions. We report on the investigation of the stabilizing effects of a denatured bovine serum albumin (dBSA) protein corona formed on the surface of upconversion nanoparticles (UCNPs). UCNPs were chosen as a nanoparticle model due to their unique photoluminescent properties suitable for background-free biological imaging and sensing. UCNP surface was modified with nitrosonium tetrafluoroborate (NOBF4) to render it hydrophilic. UCNP-NOBF4 nanoparticles were incubated in dBSA solution to form a dBSA corona followed up by lyophilization. As produced dBSA-UCNP-NOBF4 demonstrated high photoluminescence brightness, sustained colloidal stability after long-term storage and the reduced level of serum protein surface adsorption. These results show promise of dBSA-based nanoparticle pretreatment to improve the amiability to biological environments towards theranostic applications