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Although cancer stem cells have been well characterized in numerous malignancies, the fundamental characteristics of this group of cells, however, have been challenged by some recent observations: cancer stem cells may not necessary to be rare within tumors; cancer stem cells and non-cancer stem cells may undergo reversible phenotypic changes; and the cancer stem cells phenotype can vary substantially between patients. Here the current status and progresses of cancer stem cells theory is illustrated and via providing a panoramic view of cancer therapy, we addressed the recent controversies regarding the feasibility of cancer stem cells targeted anti-cancer therapy.

Synthesis of novel zwitterionic block copolypeptides, poly(N-isopropylacrylamide)-block-poly(L-glutamic acid-co-L-lysine) [PNiPAM(n)(PLG(x)-co-PLLys(y))m , where n is the number-average degree of polymerization (DP(n)) of PNiPAM block, x and y are the mole fraction of glutamic acid and lysine residues, respectively, and m is the total DP(n) of the peptide block], and their stimuli-responsiveness to temperature and pH variation in aqueous solutions are described. Initiated with the amino-terminated poly(N-isopropylacrylamide) (PNiPAM(n)-NH2), ring-opening polymerization (ROP) of a mixture of gamma-benzyl-L-glutamate N-carboxyanhydride (BLG-NCA), and Boc-L-lysine N-carboxyanhydride (BLLys-NCA) afforded the block copolypeptides PNiPAM(n)(PBLG(x)-co-PBLLys(y))m, with a poly(N-isopropylacrylamide) block together with a random copolypeptide block, which was then deprotected with HBr/trifluoroacetic acid into the double hydrophilic block copolypeptides, PNiPAM(n)(PLG(x)-co-PLLys(y))m. Their block ratios and lengths, as well as the amino acid residue ratios in the random copolypeptide block are varied (n = 360, x = 0.4-0.5, y = 0.4-0.6, and m = 220-252). The secondary structures of the copolypeptides in aqueous solution at different pH conditions were examined. Phase transitions in aqueous solutions induced by both pH and temperature variation were investigated by (1)H NMR spectroscopy. The transitions induced by temperature were also explored by turbidity measurements using UV/vis spectroscopy for their lower critical aggregation temperature (LCAT) determination. Furthermore, these aggregation processes were followed by dynamic light scattering measurements.

No abstract

Chemotherapy-resistant cancer stem cells (CSCs) are a major obstacle to the effective treatment of many forms of cancer. To overcome CSC chemo-resistance, we developed a novel system by conjugating a CSC-targeting EpCAM aptamer with doxorubicin (Apt-DOX) to eliminate CSCs. Incubation of Apt-DOX with colorectal cancer cells resulted in high concentration and prolonged retention of DOX in the nuclei. Treatment of tumour-bearing xenograft mice with Apt-DOX resulted in at least 3-fold more inhibition of tumour growth and longer survival as well as a 30-fold lower frequency of CSC and a prolonged longer tumourigenic latency compared with those receiving the same dose of free DOX. Our data demonstrate that a CSC-targeting aptamer is able to transform a conventional chemotherapeutic agent into a CSC-killer to overcome drug resistance in solid tumours.

CD63, a member of transmembrane-4-superfamily of tetraspanin proteins and a highly N-glycosylated type III lysosomal membrane protein, is known to regulate malignancy of various types of cancers such as melanoma and breast cancer and serves as a potential marker for cancer detection. Recently, its important role as a classic exosome marker was also emphasized. In this work, via using a magnetic bead-based competitive SELEX (systematic evolution of ligands by exponential enrichment) procedure and introducing a 0.5M NaCl as elution buffer, we identified two DNA aptamers (CD63-1 and CD63-2) with high affinity and specificity to CD63 protein (Kd = 38.71nM and 78.43, respectively). Furthermore, CD63-1 was found to be efficient in binding CD63 positive cells, including breast cancer MDA-MB-231 cells and CD63-overexpressed HEK293T cells, with a medium binding affinity (Kd~ 100 nM) as assessed by flow cytometry. When immunostaining assay was performed using clinical breast cancer biopsy, the CD63-1 aptamer demonstrated a comparable diagnostic efficacy for CD63 positive breast cancer with commercial antibodies. After developing a magnetic bead-based exosome immunoaffinity separation system using CD63-1 aptamer, it was found that this bead-based system could effectively isolate exosomes from both MDA-MB-231 and HT29 cell culture medium. Importantly, the introduction of the NaCl elution in this work enabled the isolation of native exosomes via a simple 0.5M NaCl incubation step. Based on these results, we firmly believe that the developed aptamers could be useful towards efficient isolation of native state exosomes from clinical samples and various theranostic applications for CD63-positive cancers.

No abstract

A series of chiral PCN pincer Pd(II) complexes VI-XIII with aryl-based aminophosphine-imidazoline or phosphinite-imidazoline ligands were synthesized and characterized. They were examined as enantioselective catalysts for the hydrophosphination of enones. Among them, complex IX, which features a Ph2PO donor as well as an imidazoline donor with (4S)-phenyl and N-Tol-p groups, was found to be the optimal catalyst. Thus, in the presence of 2-5 mol % of complex IX a wide variety of enones reacted smoothly with diarylphosphines to give the corresponding chiral phosphine derivatives in high yields with enantioselectivities of up to 98% ee. In particular, heteroaryl species such as 2-thienyl-, 2-furyl-, and 2-pyridinyl-containing enones that have a strong coordination ability to the Pd center were also appropriate substrates for the current catalytic system. For example, hydrophosphination of 2-alkenoylpyridines with diphenylphosphine followed by oxidation with H2O2 afforded the corresponding pyridine-functionalized chiral phosphine oxides in good yields with good to excellent enantioselectivities (10 examples, up to 95% ee). Furthermore, it had been demonstrated that the obtained pyridine-containing phosphine oxide acted as a tridentate ligand in the reaction with PdCl2 to form an intriguing NCsp(3)O pincer Pd(II) complex via Csp(3)-H bond activation, which to our knowledge is the first example of a chiral DCsp(3)D' Pd pincer (D ≠ D'; D and D' denote donor atoms such as P, N, etc.).