3 research outputs found
Cu<sub>2–<i>x</i></sub>S Nanocrystals Cross-Linked with Chlorin e6-Functionalized Polyethylenimine for Synergistic Photodynamic and Photothermal Therapy of Cancer
Achieving
an integrated system for combinational therapy of cancer
with enhanced efficacy is always a challenge. A multifunctional system
(CCeT nanoparticles (NPs)) for a synergistic photodynamic and photothermal
cancer therapy was successfully developed. This system is composed
of Cu<sub>2–<i>x</i></sub>S nanoclusters functionalized
with chlorin e6 (Ce6)-conjugated branched polyethylenimine (PEI-Ce6)
and mitochondria-targeting 3-(carboxypropyl)Âtriphenylphosphonium bromide
(TPP-COOH). The colocalization of the resulted CCeT NPs inside the
mitochondria of cancer cells was proven. The CCeT NPs exhibited significant
photodynamic therapy (PDT) efficacy due to efficient singlet oxygen
(<sup>1</sup>O<sub>2</sub>) generation triggered by a 630 nm laser.
This system also showed excellent photothermal conversion capability
upon the irradiation of 808 nm laser for photothermal therapy (PTT).
In particular, the platform achieved nearly 100% inhibitory rate of
the tumor growth in vivo through combinational PDT and PTT. Thus,
the CCeT NPs could efficiently inhibit the tumor growth in vitro and
in vivo by combinational PDT and PTT, offering synergistic therapeutic
efficiency as compared to PTT or PDT alone
Combined Photodynamic and Photothermal Therapy Using Cross-Linked Polyphosphazene Nanospheres Decorated with Gold Nanoparticles
A rational
combination of photodynamic therapy (PDT) and photothermal
therapy (PTT) could achieve a synergistic therapeutic effect to enhance
therapeutic efficacy in the cancer treatment. Herein, polyphosphazene
nanospheres as a novel kind of photosensitizer carriers were synthesized
by anchoring and isolating photosensitizing porphyrin monomers covalently
in the cross-linked structure. Gold nanoparticles were then immobilized
on the surface of the nanospheres to introduce the photothermal performance.
The hybrid system was eventually conjugated by polyethylene glycol
to decrease its cytotoxicity. The morphology analysis showed that
the nanospheres were covered by homogeneously dispersed gold nanoparticles.
In this way, the resulted system could afford efficient photodynamic
and photothermal effect simultaneously, as confirmed by the cancer
cell killing studies. The cell experiments demonstrated that the as-prepared
polyphosphazene nanospheres with inherent fluorescence could be internalized
by HeLa cells, showing high performance of combined PDT and PTT under
suitable light irradiation. Thus, this integrated system presents
its effectiveness to achieve combined PDT and PTT for enhanced cancer
therapeutics
Theranostic Prodrug Vesicles for Imaging Guided Codelivery of Camptothecin and siRNA in Synergetic Cancer Therapy
The
construction of prodrugs has been a popular strategy to overcome the
limitations of chemotherapeutic drugs. However, complicated synthesis
procedures and laborious purification steps make the fabrication of
amphiphilic prodrugs rather difficult. By harnessing the concept of
host–guest interaction, we designed and prepared a supra-amphiphile
consisting of a dendritic cyclodextrin host and an adamantane/naphthalimide-modified
camptothecin guest through glutathione-responsive disulfide linkage.
This host–guest complex could self-assemble in aqueous solution
to give nanosized vesicles. When the disulfide bond in adamantane/naphthalimide-modified
camptothecin was cleaved by glutathione, the fluorescence of the freed
adamantane/naphthalimide unit showed a significant red shift with
enhanced intensity. Such glutathione-responsive fluorescence change
allows for intracellular imaging and simultaneous monitoring of drug
release in real time. On account of abundant positively charged amine
groups on the supramolecular vesicle surface, siRNA (siPlK1) could
be efficiently loaded on the vesicle. The gel retardation and fluorescence
experiments proved that the siPlK1 was successfully bonded to the
supramolecular vesicle. The vesicle with dendritic cyclodextrin ring
exhibited negligible cytotoxicity even at high concentrations, avoiding
the shortcoming of cytotoxicity from commonly used gene vectors. In
vitro studies demonstrated that the loaded siRNA was transported into
cancer cells to improve cancer therapeutic efficacy. Thus, we developed
a prodrug-based supramolecular amphiphile via the host–guest
interaction with better therapeutic performance than free camptothecin.
The assembled system was utilized as a drug/gene vector to achieve
combinational gene therapy and chemotherapy with a synergistic effect,
providing an alternative strategy to deliver both prodrug and therapeutic
gene