title: Real-Time Monitoring of ATP-Responsive Drug Release Using Mesoporous-Silica-Coated Multicolor Upconversion Nanoparticles.
abstract: Stimuli-responsive drug delivery vehicles have garnered immense interest in recent years due to unparalleled progress made in material science and nanomedicine. However, the development of stimuli-responsive devices with integrated real-time monitoring capabilities is still in its nascent stage because of the limitations of imaging modalities. In this paper, we describe the development of a polypeptide-wrapped mesoporous-silica-coated multicolor upconversion nanoparticle (UCNP@MSN) as an adenosine triphosphate (ATP)-responsive drug delivery system (DDS) for long-term tracking and real-time monitoring of drug release. Our UCNP@MSN with multiple emission peaks in UV-NIR wavelength range was functionalized with zinc-dipicolylamine analogue (TDPA-Zn(2+)) on its exterior surface and loaded with small-molecule drugs like chemotherapeutics in interior mesopores. The drugs remained entrapped within the UCNP-MSNs when the nanoparticles were wrapped with a compact branched polypeptide, poly(Asp-Lys)-b-Asp, because of multivalent interactions between Asp moieties present in the polypeptide and the TDPA-Zn(2+) complex present on the surface of UCNP-MSNs. This led to luminescence resonance energy transfer (LRET) from the UCNPs to the entrapped drugs, which typically have absorption in UV-visible range, ultimately resulting in quenching of UCNP emission in UV-visible range while retaining their strong NIR emission. Addition of ATP led to a competitive displacement of the surface bound polypeptide by ATP due to its higher affinity to TDPA-Zn(2+), which led to the release of the entrapped drugs and subsequent elimination of LRET. Monitoring of such ATP-triggered ratiometric changes in LRET allowed us to monitor the release of the entrapped drugs in real-time. Given these results, we envision that our proposed UCNP@MSN-polypeptide hybrid nanoparticle has great potential for stimuli-responsive drug delivery as well as for monitoring biochemical changes taking place in live cancer and stem cells.
authors: Department of Chemistry and Chemical Biology, Institute for Advanced Materials, Devices and Nanotechnology (IAMDN), Rutgers University, Piscataway, New Jersey 08854, United States.
authors: Jinping
authors: J
authors: Lai
authors: Department of Chemistry and Chemical Biology, Institute for Advanced Materials, Devices and Nanotechnology (IAMDN), Rutgers University, Piscataway, New Jersey 08854, United States.
authors: Birju P
authors: BP
authors: Shah
authors: Department of Chemistry and Chemical Biology, Institute for Advanced Materials, Devices and Nanotechnology (IAMDN), Rutgers University, Piscataway, New Jersey 08854, United States.
authors: Yixiao
authors: Y
authors: Zhang
authors: Department of Chemistry and Chemical Biology, Institute for Advanced Materials, Devices and Nanotechnology (IAMDN), Rutgers University, Piscataway, New Jersey 08854, United States.
authors: Letao
authors: L
authors: Yang
authors: Department of Chemistry and Chemical Biology, Institute for Advanced Materials, Devices and Nanotechnology (IAMDN), Rutgers University, Piscataway, New Jersey 08854, United States.
authors: Ki-Bum
authors: KB
authors: Lee
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000588:Amines / Q000737:chemistry; D003116:Color; D004317:Doxorubicin / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D004735:Energy Transfer; D006801:Humans; D061986:MCF-7 Cells; D050997:Nanomedicine; D053758:Nanoparticles / Q000737:chemistry*; D009842:Oligopeptides / Q000737:chemistry; D010848:Picolinic Acids / Q000737:chemistry; D016062:Porosity; D012822:Silicon Dioxide / Q000737:chemistry*; D015032:Zinc / Q000737:chemistry
chemical_list: C501847:2,2'-dipicolylamine; D000588:Amines; D004337:Drug Carriers; D009842:Oligopeptides; D010848:Picolinic Acids; D012822:Silicon Dioxide; D004317:Doxorubicin; D000255:Adenosine Triphosphate; D015032:Zinc
keywords: core−shell nanoparticles; luminescence resonance energy transfer (LRET); real-time monitoring; stimuli-responsive drug delivery; upconversion nanoparticle