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Biotin receptors are overexpressed by various types of solid cancer cells and play a significant role in tumor metabolism, growth, and metastasis. Thus, targeting the biotin receptors on tumor cells may enhance the efficiency and reduce the side-effects of chemotherapy. The aim of this study was to develop a biotin-coupled poly(amido)amine (PAMAM) (PG4.5) dendrimer nanoparticle to enhance the tumor-specific delivery and intracellular uptake of anticancer drugs via receptor-mediated endocytosis. We modified PG4.5 with diethylenetriamine (DETA) followed by biotin via an amide bond and characterized the resulting PG4.5-DETA-biotin nanoparticles by 1H NMR, FTIR, and Raman spectroscopy. Loading and releasing of gemcitabine (GEM) from PG4.5-DETA-biotin were evaluated by UV–Visible spectrophotometry. Cell viability and cellular uptake were examined by MTT assay and flow cytometry to assess the biocompatibility, cellular internalization efficiency and antiproliferative activity of PG4.5-DETA-biotin/GEM. Gemcitabine-loaded PG4.5-DETA-biotin nanoparticles were spherical with a particle size of 81.6 ± 6.08 nm and zeta potential of 0.47 ± 1.25 mV. Maximum drug-loading content and encapsulation efficiency were 10.84 ± 0.16% and 47.01 ± 0.71%, respectively. Nearly 60.54 ± 1.99% and 73.96 ± 1.14% of gemcitabine was released from PG4.5-DETA-biotin/GEM nanoparticles after 48 h at the acidic pH values of 6.5 and 5, respectively. Flow cytometry and fluorescence microscopy of cellular uptake results revealed PG4.5-DETA-biotin/GEM nanoparticles selectively targeted cancer cells in vitro. Cytotoxicity assays demonstrated gemcitabine-loaded PG4.5-DETA-biotin significantly reduced cell viability and induced apoptosis in HeLa cells. Thus, biotin-coupled PG4.5-DETA nanocarrier could provide an effective, targeted drug delivery system and selectively convey gemcitabine into tumor cells.

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Purpose In this study, the 188 Re-labeled PEGylated nanoliposome ( 188 Re-liposome) was prepared and evaluated as a therapeutic agent for glioma. Materials and methods The reporter cell line, F98 luc was prepared via Lentivector expression kit system and used to set up the orthotopic glioma-bearing rat model for non-invasive bioluminescent imaging. The maximum tolerated dose applicable in Fischer344 rats was explored via body weight monitoring of the rats after single intravenous injection of 188 Re-liposome with varying dosages before the treatment study. The OLINDA/EXM 1.1 software was utilized for estimating the radiation dosimetry. To assess the therapeutic efficacy, tumor-bearing rats were intravenously administered 188 Re-liposome or normal saline followed by monitoring of the tumor growth and animal survival time. In addition, the histopathological examinations of tumors were conducted on the 188 Re-liposome-treated rats. Results By using bioluminescent imaging, the well-established reporter cell line (F98 luc ) showed a high relationship between cell number and its bioluminescent intensity ( R 2 =0.99) in vitro; furthermore, it could also provide clear tumor imaging for monitoring tumor growth in vivo. The maximum tolerated dose of 188 Re-liposome in Fischer344 rats was estimated to be 333 MBq. According to the dosimetry results, higher equivalent doses were observed in spleen and kidneys while very less were in normal brain, red marrow, and thyroid. For therapeutic efficacy study, the progression of tumor growth in terms of tumor volume and/or tumor weight was significantly slower for the 188 Re-liposome-treated group than the control group ( P <0.05). As a result, the lifespan of glioma-bearing rats treated with 188 Re-liposome was prolonged 10.67% compared to the control group. Conclusion The radiotherapeutic evaluation by dosimetry and survival studies have demonstrated that passive targeting 188 Re-liposome via systemic administration can significantly prolong the lifespan of orthotopic glioma-bearing rats while maintaining reasonable systemic radiation safety. Therefore, 188 Re-liposome could be a potential therapeutic agent for glioblastoma multiforme treatment.

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required for successful cancer metastasis are: detachment of cancer cells from the primary mass, invasion of the local host tissue stroma, penetration of local lymphatic and blood vessels, survival during circulation, arrest in the capillaries of other organs, formation of microemboli, extravasation, and proliferation within the organ parenchyma. [8][9][10][11] The main challenges for metastasis treatment are systemic complexity, therapeutic resistance, and difficulty in early diagnosis. [10] Currently, there are no medicines available to specifically prevent cancer cell metastasis, but the development of inhibitory agents that selectively suppress or block metastasis-associated mechanisms provide an alternative for metastatic treatments. [12,13] Anti-metastasis therapy mainly focuses on interrupting the metastatic cascade of tumor cells. Even if the types of therapy depend on the timing of diagnosis, the typical anti-metastasis strategies are designed to block the initiation of metastasis, intercept and eradicate circulating tumor cells, and limit the formation of tumor cell colonies at distant organs. [14] For instance, MMP inhibitors, the Axl kinase inhibitor R428, miR-10b antagonists, and the fascin inhibitor Migrastatin are used as anti-metastatic agents for impairing the initial dissemination events. However effective anti-metastatic therapeutic agents must be capable of destroying the proliferation and survival of already disseminated tumor cells, rather than only seeking to block the exit of these cells from the primary tumor. [8] Treatments that involve a targeted sustained release of chemotherapeutic agents are the most prevalent approach to cancer treatment and inhibition of tumor metastasis. [15] Studies on cancer research have investigated hydrogels, nanoparticles, micelles, and liposomes for enhancing the efficacy of tumor treatment. Current studies on polymer-based tumor therapeutic systems focus on achieving the following goals: 1) providing anti-metastatic effects, 2) specific drug release in the tumor tissue, 3) enhanced antitumor efficacy, and 4) good biocompatibility and biodegradable properties of the nanoparticles. [16] Nevertheless, intravenous administration of therapeutic agents often leads to adverse systemic effects and rapid clearance from the circulating blood. Furthermore, frequent administration of anti-metastatic agents Injectable HydrogelsMetastasis is a pathogenic spread of cancer cells from the primary site to surrounding tissues and distant organs, making it one of the primary challenges for effective cancer treatment and the major cause of cancer mortality. Heparin-based biomaterials exhibit significant inhibition of cancer cell metastasis. In this study, a non-anticoagulate heparin prodrug is developed for metastasis treatment with a localized treatment system using temperature sensitive, injectable, and biodegradable (poly-(ε-caprolactone-co-lactide)-bpoly(ethylene glycol)-b-poly(ε-caprolactone-co-lactide) polymeric hydrogel. The drug molecule (heparin) is conjugated with th...

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