CX-5461-loaded nucleolus-targeting nanoplatform for cancer therapy through induction of pro-death autophagy

Acta Biomaterialia
Yanhong DuoHongbo Chen

Abstract

Various drugs have been designed in the past to act on intracellular targets. For the desired effects to be exerted, these drugs should reach and accumulate in specific subcellular organelles. CX-5461 represents a potent small-molecule inhibitor of rRNA synthesis that specifically inhibits the transcription driven by RNA polymerase (Pol) I and induces tumor cell death through triggering a pro-death autophagy. In the current study an innovative kind of CX-5461-loaded mesoporous silica nano-particles enveloped by polyethylene glycol (PEG), polydopamine (PDA) and AS-1411 aptamer (MSNs-CX-5461@PDA-PEG-APt) with the aim of treating cancer cells was constructed, in which the high-surface-area MSNs allowed for high drug loading, PDA acted as gatekeeper to prevent the leakage of CX-5461 from MSNs, PEG grafts on PDA surfaces increased the stable and biocompatible property in physiological condition, and AS-1411 aptamer promoted the nucleolar accumulation of CX-5461. MSNs-CX-5461@PDA-PEG-APt was characterized regarding releasing characteristics, steadiness, encapsulation of drugs, phase boundary potential as well as sizes of particles. Expectedly, In vitro assays showed that aptamer AS-1411 significantly increased the nucleolar accumulat...Continue Reading

Citations

May 23, 2019·Frontiers in Cellular Neuroscience·Astrid S Pfister
Jan 8, 2020·Current Drug Delivery·Garima ShrivastavaMurtaza M Tambuwala
Sep 29, 2019·Biomolecules·Shima TavakolAlan Prem Kumar
Oct 7, 2020·International Journal of Molecular Sciences·Annalisa PecoraroAnnapina Russo
Aug 24, 2019·Seminars in Cancer Biology·Abul BarkatFarhan J Ahmed
May 5, 2021·Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology·Peijie ZhouDong Qian
May 26, 2021·Expert Opinion on Drug Delivery·Eder Lilia Romero, Maria Jose Morilla
Jun 27, 2021·Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology·Reshma Vasantha RamachandranAmbarish Ghosh

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