Efficient drug delivery to tumors is of ever increasing importance. Single-visit diagnosis and treatment sessions are the goal of future theranostics. In this paper, a non-covalent PDT cancer drug-gold nanoparticle (Au NP) conjugate system performed a rapid drug release and deep penetration of the drug into tumors within hours. The drug delivery mechanism of the PDT drug through Au NPs into tumors by passive accumulation was investigated via fluorescence imaging, elemental analysis, and histological staining. The pharmacokinetics of the conjugates over a 7 day test period showed fast drug excretion, as monitored via the fluorescence of the drug in urine. Moreover, the biodistribution of Au NPs in this study period indicated clearance of the NPs from the mice. This study suggests that the non-covalent delivery via Au NPs provides an attractive approach for cancer drugs to penetrate deep into the center of tumors.
Six new aluminum and silicon phthalocyanines have been synthesized and their photocytotoxicity toward V79 cells has been studied. The compounds that have been prepared are: A1PcOSi(CH3)2(CH2)3N(CH3)2, I; A1Pc-OSi(CH3)2(CH2)3N(CH3)3+I-, II; CH3SiPcOSi(CH3)2(CH2)3N(CH3)2, III; HOSiPcOSi(CH3)2(CH2)3N(CH3)2, IV; HOSiPcOSi(CH3)2(CH2)3N(CH3)3+I-, V; and SiPc[OSi(CH3)2(CH2)3N(CH3)3+I-]2, VI. Relative growth delay values for compounds I-VI and relative cytotoxicity values for compounds I, II, IV, V and VI have been determined. Compounds I and II have been shown to be comparable in photocytotoxicity to what is presumed to be A1PcOH.xH2O, and compound IV has been shown to have greater activity. The classes of compounds to which these six compounds belong appear to have potential for photodynamic therapy.
Reported herein is a combination of experimental and DFT/TDDFT theoretical investigations of the ground and excited states of 1,4,8,11,15,18,22,25-Octabutoxyphthalocyaninato-nickel(II), NiPc(BuO)(8), and the dynamics of its deactivation after excitation into the S(1)(pi,pi) state in toluene solution. According to X-ray crystallographic analysis NiPc(BuO)(8) has a highly saddled structure in the solid state. However, DFT studies suggest that in solution the complex is likely to flap from one D(2)(d)-saddled conformation to the opposite one through a D(4)(h)-planar structure. The spectral and kinetic changes for the complex in toluene are understood in terms of the 730 nm excitation light generating a primarily excited S(1) (pi,pi) state that transforms initially into a vibrationally hot (3)(d(z)2,d(x)2(-)(y)2) state. Cooling to the zeroth state is complete after ca. 8 ps. The cold (d,d) state converted to its daughter state, the (3)LMCT (pi,d(x)2(-)(y)2), which itself decays to the ground state with a lifetime of 640 ps. The proposed deactivation mechanism applies to the D(2)(d)-saddled and the D(4)(h)-planar structure as well. The results presented here for NiPc(BuO)(8) suggest that in nickel phthalocyanines the (1,3)LMCT (pi,d(x)2(-)(y)2) states may provide effective routes for radiationless deactivation of the (1,3)(pi,pi) states.
EGF‐modified Au NP–Pc 4 conjugates showed 10‐fold improved selectivity to the brain tumor compared to untargeted conjugates. The hydrophobic photodynamic therapy drug Pc 4 can be delivered efficiently into glioma brain tumors by EGF peptide‐targeted Au NPs. Compared to the untargeted conjugates, EGF–Au NP–Pc 4 conjugates showed 10‐fold improved selectivity to the brain tumor. This delivery system holds promise for future delivery of a wider range of hydrophobic therapeutic drugs for the treatment of hard‐to‐reach cancers.
Therapeutic drug delivery across the blood-brain barrier (BBB) is not only inefficient, but also nonspecific to brain stroma. These are major limitations in the effective treatment of brain cancer. Transferrin peptide (Tfpep) targeted gold nanoparticles (Tfpep-Au NPs) loaded with the photodynamic pro-drug, Pc 4, have been designed and compared with untargeted Au NPs for delivery of the photosensitizer to brain cancer cell lines. In vitro studies of human glioma cancer lines (LN229 and U87) overexpressing the transferrin receptor (TfR) show a significant increase in cellular uptake for targeted conjugates as compared to un-targeted particles. Pc 4 delivered from Tfpep-Au NPs clusters within vesicles after targeting with the Tfpep. Pc 4 continues to accumulate over a 4 hour period. Our work suggests that TfR-targeted Au NPs may have important therapeutic implications for delivering brain tumor therapies and/or providing a platform for noninvasive imaging.
The synthesis, spectral characterization, and electrochemical behavior of bis(tri-n-hexylsiloxy)(2,3-phthalocyaninato)silicon [SiPc(OR)2], its dimer [RO(SiPcO)2R], and its naphthalocyanine analogue [SiNc(OR)2] are described. All compounds show near-UV absorption corresponding to Soret and N bands and intense absorption in the visible-near-IR region corresponding to Q bands. In CH2C12, within the solvent stability limit, there are two reductions and one oxidation for SiPc(OR)2 and two reductions and two oxidations for RO(SiPcO)2R and SiNc(OR)2; all appear as reversible one-electron waves, although = 2 for the dimer. The difference in the peak potentials of the first oxidation and first reduction waves agrees well with the excitation energy and fluorescence (corresponding to Q bands) of SiPc(OR)2 and SiNc(OR)2. Both compounds emit upon electrochemical generation of reduced and oxidized forms (electrogenerated chemiluminescence, eel). The corrected eel maxima are near 684 nm for SiPc(OR)2 and 792 nm for SiNc(OR)2; the latter corresponds to the longest wavelength eel emission reported so far. The phthalocyanine dimer, RO(SiPcO)2R, is easier to reduce and easier to oxidize than the monomer.The voltammetric waves in this case involve two-electron transfers with peak splittings characteristic of le waves, suggesting that the two phthalocyanine rings in the dimer do not strongly interact. No fluorescence or eel was observed from the dimer.Phthalocyanine compounds often show high thermal and chemical stability and interesting optical and electrical properties.1"5 67We and others have been interested in the conductivities
In this feature article, gold nanoparticle conjugates loaded with phthalocyanine-based PDT drugs are prepared and tested for delivery efficiency and PDT efficacy on HeLa cancer cells. It could be shown that the delivery and PDT outcome are strongly affected by the bond that links the drug load to the nanoparticle surface. Whereas labile amino adsorption to the Au nanoparticle surface allows for efficient drug release into the cancer cells and for efficient PDT, a covalent thiol bond to the Au nanoparticle leads to the delivery of the drug into cell vesicles, and no PDT effect is observed. This work highlights the importance of carefully choosing the interaction between drug molecules and the nanoparticle surface.
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