DNA-assembled visible nanodandelions with explosive hydrogen-bond breakage achieving uniform intra-tumor distribution (UITD)-guided photothermal therapy.

Photothermal therapy (PTT) has received increasing attention for treating tumors. However, a long-standing challenge in PTT is non-uniform distribution of photothermal agents (PAs) in tumor tissues, resulting in limited therapeutic efficiency. Herein, inspired by dandelions blowing away by the wind, we have designed a DNA-assembled visible GRS-DNA-CuS nanodandelion, which can achieve uniform intra-tumor distribution (UITD) of PAs, thus enhancing the photothermal therapeutic efficiency. GRS-DNA-CuS is featured by the formation of hydrogen bond between the core of single-strand DNA-modified Raman nanoprobes (GRS) and the shell of complementary single-strand DNA-modified CuS PAs. Under Raman imaging-guided 1st NIR irradiation, hydrogen bond in GRS-DNA-CuS is explosively broken, resulting in large-sized GRS-DNA-CuS (∼135 nm) be completely dissociated into GRS and ultra-small CuS PAs (∼12 nm) within 1 min. Such an explosive dissociation instantly enhances the local concentration of ultra-small CuS PAs and slightly rises intra-tumor temperature, thus increasing the diffusion coefficient of PAs and promoting their UITD. This UITD of CuS PAs enhances the photothermal anti-tumor effects. Three out of five tumors are completely eliminated under photoacoustic imaging-guided 2nd NIR irradiation. Overall, this study provides one UITD-guided PTT strategy for highly effective tumor treatment by exerting explosive breakage property of hydrogen bond, broadening the application scope of DNA-assembly technique in oncology field.

Dual-Targeting Magnetic PLGA Nanoparticles for Codelivery of Paclitaxel and Curcumin for Brain Tumor Therapy.

Chemotherapy is one of the most important strategies for glioma treatment. However, the "impermeability" of the blood-brain barrier (BBB) impedes most chemotherapeutics from entering the brain, thereby rendering very few drugs suitable for glioma therapy, letting alone application of a combination of chemotherapeutics. Thereby, there is a pressing need to overcome the obstacles. A dual-targeting strategy was developed by a combination of magnetic guidance and transferrin receptor-binding peptide T7-mediated active targeting delivery. The T7-modified magnetic PLGA nanoparticle (NP) system was prepared with co-encapsulation of the hydrophobic magnetic nanoparticles and a combination of drugs (i.e., paclitaxel and curcumin) based on a "one-pot" process. The combined drugs yielded synergistic effects on inhibition of tumor growth via the mechanisms of apoptosis induction and cell cycle arrest, displaying significantly increased efficacy relative to the single use of each drug. Dual-targeting effects yielded a >10-fold increase in cellular uptake studies and a >5-fold enhancement in brain delivery compared to the nontargeting NPs. For the in vivo studies with an orthotopic glioma model, efficient brain accumulation was observed by using fluorescence imaging, synchrotron radiation X-ray imaging, and MRI. Furthermore, the antiglioma treatment efficacy of the delivery system was evaluated. With application of a magnetic field, this system exhibited enhanced treatment efficiency and reduced adverse effects. All mice bearing orthotopic glioma survived, compared to a 62.5% survival rate for the combination group receiving free drugs. This dual-targeting, co-delivery strategy provides a potential method for improving brain drug delivery and antiglioma treatment efficacy.