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A series of pegylated cis-A₂B₂- or A₃B-type ZnPcs, substituted on the α-positions with tri(ethylene glycol) and hydroxyl groups, were synthesized from a new bis-phthalonitrile. A clamshell-type bis-phthalocyanine was also obtained as a byproduct. The hydroxyl group of one ZnPc was alkylated with 3-dimethylaminopropyl chloride to afford a pegylated ZnPc functionalized with an amine group. All mononuclear ZnPcs were soluble in polar organic solvents, showed intense Q absorptions in DMF, and had fluorescence quantum yields in the range 0.10–0.23. The clamshell-type bis-phthalocyanine adopts mainly open shell conformations in DMF, and closed clamshell conformations in chloroform. All ZnPcs were highly phototoxic to human carcinoma HEp2 cells, particularly the amino-ZnPc mainly protonated under physiological conditions, which showed the highest phototoxicity (IC₅₀ = 0.5 μM at 1.5 J/cm²) dark cytotoxicity (IC₅₀ = 22 μM), in part due to its high cellular uptake. The ZnPcs localized in multiple organelles, including mitochondria, lysosomes, Golgi and ER.

A series of boron-functionalized BODIPY dyes with cyano groups were prepared from their corresponding BF₂ derivatives using SnCl₄/TMSCN at room temperature for 10 min. Replacement of the fluorines by cyano groups reduces the B–N bond lengths, decreases the charge on boron, and causes characteristic ${}^{11}$B NMR chemical shifts. The 4,4${}^{\prime }$-dicyano-BODIPYs show significantly enhanced stability to acidic conditions (excess TFA) and, with one exception, enhanced fluorescence quantum yields. Furthermore, the B(CN)₂-BODIPYs were non-cytotoxic to HEp2 cells, both in the dark and upon exposure to light (1.5 J/cm${}^2)$, and rapidly accumulated within cells, localizing mainly in the lysosomes, ER and Golgi.

Photosensitizers currently used for photodynamic therapy of cancer show enhanced accumulation in tumor tissue but lack cancer cell specificity. To augment cellular uptake, the targeting of pyropheophorbide-a to carbohydrate-binding components of cancer cells was explored. Galactose was attached to pyropheophorbide-a at positions 17² and 20. Since the modification at position 17² removed a carboxylic group, which is relevant for cell specificity, this study evaluated the relative contribution of galactosyl and carboxyl groups at either position 17² or 20, with or without a (hexyloxy)ethyl at position 3, to cellular uptake by human epithelial cancer cells. The subcellular deposition was monitored using fluorescence microscopy and the photoreaction was quantified using biomarkers. The results demonstrated that any galactose addition suppresses transmembrane diffusion and promotes endocytosis and lysosomal accumulation. An anionic group at position 17² or 20 enhances lysosomal retention. Neutralization of the carboxylic group at position 17² facilitates transfer to mitochondria/endoplasmatic reticulum and promotes tumor cell-specific retention. Replacing (hexyloxy)ethyl with an ethyl group at position 3 increased both cellular uptake and egress but did not alter subcellular localization. These findings suggest that specific neutral galactosylated pheophorbides may provide an enhanced therapeutic effect for those tumor types that do not retain unmodified pyropheophorbide. However, the galactose conjugates also serve as substrates for preferential uptake by liver cells resulting in hepatic sequestration, reduced systemic distribution, and lower accumulation in tumor tissue.

Magnetic nanoparticles (MNPs) used in bio-application have accelerated the development of “theranostics” which contains imaging, therapy and drug delivery. However, in a protein-rich physiological fluid, MNPs are ineluctable to a contact with protein to form “protein corona”, which will significantly change the physicochemical properties of the particles and their biological behavior. Therefore, we investigated the influence of protein and static magnetic field (SMF) on the cytotoxicity and cellular uptake of MNPs. The Fe₃O₄ nanoparticles (Fe₃O₄ NPs) were synthesized by solvothermal method with a mean diameter of $\sim 100$nm functionalized with carboxyl groups. After a period of 12h incubation in complete medium (CM), the wrapping of the Fe₃O₄ NPs by protein adsorption resulted in about 40-nm increase of the hydrodynamic size. Their stability in CM and water solution did not broaden significantly over time, which is exactly opposite in serum-free media (SFM). When transferred to SFM with high ionic-strength, the Fe₃O₄ NPs aggregated and settled quickly. We explore that the cell viability was decreased in proportion to the concentration and incubating time of Fe₃O₄ NPs, the absence of FBS and the presence of SMF exposure, respectively. Quantitative analysis showed that cells could incorporate more NPs in SFM, about five-fold more than in CM. In addition, it is obvious that exposure to SMF resulted in more cellular uptake both in CM and SFM. Our results demonstrated that Fe₃O₄ NPs in SFM and SMF exposure would settle down to cell rapidly, which caused more cellular uptake and higher cytotoxicity.

In order to define the ability of layered double hydroxide (LDH) as materials for drug delivery, fluorescein (Fluo) anion intercalated LDH (Fluo/LDH) was synthesized by hydrothermal treatment and observed the cellular uptake of the Fluo/LDH for mammalian cell (L929). The synthesized Fluo/LDH showed a LDH structure, high fluorescence and low cytotoxicity. According to the fluorescence, confocal and TEM images of cells, the Fluo/LDH seemed to be internalized into the L929 cell by cellular endocytosis and dissolved inside the cell to exhibit the fluorescence of cellular cytoplasm.

Phenylethyl resorcinol-loaded cationic nanoliposomes (PR-CLPs) were prepared and characterized. Moreover, their transdermal properties, cellular uptake, and inhibition of tyrosinase activity and melanin production in B16F10 cells were studied. The mean particle size, polydispersity index (PDI) and zeta potential of the PR-CLPs were $102.1\pm 1.3$nm, $0.22\pm 0.01$mV $\mathrm{\text{and}}+23.7\pm 1.7$mV, respectively. The drug loading efficiency (DLE) and entrapment efficiency (EE) of PR in the PR-CLPs were $8.8\pm 0.1$% and $90.3\pm 1.3$%, respectively. Sustained release of PR from the PR-CLPs was observed in vitro release experiments. The results of the in vitro transdermal experiments showed that PR-CLPs significantly improved both the retention of PR in the skin and its transdermal permeability ($P<0.05$) in comparison with PR solution or traditional phenylethyl resorcinol nanoliposomes (PR-LPs). The uptake and accumulation of FITC-CLPs in B16F10 cells was significantly enhanced as compared with that of FITC-LPs. Furthermore, at a PR concentration of 20 or 30$\mu$g/mL, PR-CLPs displayed a high tyrosinase inhibitory activity and caused a noticeable reduction in the melanin content in B16F10 cells. Taken together, these results indicate that PR-CLPs can efficiently deliver phenylethyl resorcinol to produce an enhanced skin lightening effect.

Erlotinib is used as first-line chemotherapy for the treatment of non-small cell lung cancer (NSCLC), which accounts for approximately 85% of lung cancers. Curcumin has potential antitumor effects in different types of cancer including NSCLS with additional chemopreventive and radioprotective effects. The aim of the study was to develop erlotinib and curcumin co-loaded dry powder inhalation (EC-DPI) formulation using nanoprecipitation technique with a goal of achieving a stronger cytotoxic effect against A549 cancer cells. The optimized DPI formulation resulted in suitable particle size (313.28 ± 26.19 nm), polydispersity index (0.156 ± 0.016) and zeta potential (29.4 ± 1.22 mV). Carr’s index (6.62 ± 1.43) and Hausner ratio (1.058 ± 0.03) demonstrated excellent flowability of the powder. The fine particle fraction (64.7 ± 7.8%) and mass median aerodynamic diameter (2.98 ± 0.04 $\mu$m) of the optimized formulation revealed good aerosol performance and its suitability for direct delivery to the lungs. In-vitro cytotoxic potential of EC-DPI was determined against A549 cancer cells and compared with curcumin-loaded DPI formulation (C-DPI) and erlotinib-loaded DPI formulation (E-DPI). The IC${}_{50}$ values for E-DPI and C-DPI were found to be 36.6 ± 2.4 $\mu$M and 24.4 ± 2.7 $\mu$M, respectively. The IC${}_{50}$ value for EC-DPI was 20.5 ± 2.1 $\mu$M confirming the synergistic effect of both drugs against A549 cancer cells. The internalization of the drug inside A549 cells was detected by a cellular uptake study. The EC-DPI demonstrated the highest cellular uptake (0.07 ± 0.006 ng/$\mu$g) followed by the formulation containing curcumin (0.05 ± 0.003 ng/$\mu$g) and erlotinib (0.03 ± 0.004 ng/$\mu$g) alone at the end of 6 h. Hence, the developed DPI formulation can be considered as a potential therapeutic approach for the direct delivery of erlotinib and curcumin to treat NSCLC.