Responsive Assembly of Upconversion Nanoparticles for pH‐Activated and Near‐Infrared‐Triggered Photodynamic Therapy of Deep Tumors

Abstract

Upconversion nanoparticle (UCNP)-mediated photodynamic therapy has shown great effectiveness in increasing the tissue-penetration depth of light to combat deep-seated tumors. However, the inevitable phototoxicity to normal tissues resulting from the lack of tumor selectivity remains as a major challenge. Here, the development of tumor-pH-sensitive photodynamic nanoagents (PPNs) comprised of self-assembled photosensitizers grafted pH-responsive polymeric ligands and UCNPs is reported. Under neutral pH conditions, photosensitizers aggregated in the PPNs are self-quenched; however, upon entry into a tumor microenvironment with lower pH, the PPNs not only exhibit enhanced tumor-cell internalization due to charge reversal but also are further disassembled into well-dispersed nanoparticles in the endo/lysosomes of tumor cells, enabling the efficient activation of photosensitizers. The results demonstrate the attractive properties of both UCNP-mediated deep-tissue penetration of light and high therapeutic selectivity in vitro and in vivo.

Tumor‐Microenvironment‐Triggered Ion Exchange of a Metal–Organic Framework Hybrid for Multimodal Imaging and Synergistic Therapy of Tumors

“…[ 1–7 ] With the development of nanotechnology, many NTAs with imaging capabilities including computed tomography (CT), magnetic resonance imaging (MRI), and photoacoustic (PA) imaging and therapeutic functions including photodynamic therapy (PDT), photothermal therapy (PTT), or chemodynamic therapy (CDT) have been extensively developed. [ 8–18 ] However, most of reported NTAs suffer from their poor tumor specificity and unsatisfactory therapeutic efficiency due to the severe background interference during metabolism caused by the “always on” model. [ 19–21 ] To solve this problem, in situ NTA synthesis strategy to activate pro‐NTAs (precursor of NTAs) into NTAs at desired locations has attracted increasing attention.…”

Enhancement of Photodynamic Cancer Therapy by Physical and Chemical Factors

“…UCNPs have been found to be chemically stable and unlike organic fluorescent dyes, UCNPs avoid traditional photobleaching complications. Recently UCNPs have been utilized as nanocarriers for photosensitizer in PDT . UCNPs have been integrated with photosensitizers including merocyanine, docetaxel, zinc phthalocyanine, chlorin e6, doxorubicin (Figure ), and pyropheophorbide a to develop PDT.…”

“…[57] UCNPs have been found to be chemically stable and unlike organic fluorescent dyes,U CNPs avoid traditional photobleaching complications.Recently UCNPs have been utilized as nanocarriers for photosensitizer in PDT. [58] UCNPs have been integrated with photosensitizers including merocyanine, [59] docetaxel, [60] zinc phthalocyanine, [61] chlorin e6, [56b] doxorubicin ( Figure 5), [62] and pyropheophorbide a [34] to develop PDT.T he resultant conjugates exhibit efficient singlet oxygen generation after NIR light exposure giving an improved therapeutic effect, both in vitro and in vivo. Furthermore,s ome groups [56b] prepared nanorattles made of ah ydrophilic rare-earth doped NaYF 4 shell and magnetic nanoparticle cores.T his material showed excellent water dispersion capability,ah igh drug-loading capacity,a nd low cytotoxicity;i twas also shown to be useful for cell imaging.…”

Optimierung photodynamischer Krebstherapien auf der Grundlage physikalisch‐chemischer Faktoren

“…Vork urzem wurden UCNPs als Nanoträger fürP hotosensibilisatoren in der PDT verwendet. [58] Fürd ie Entwicklung von PDT-Anwendungen wurden UCNPs mit Photosensibilisatoren wie Merocyanin, [59] Docetaxel, [60] Zinkphthalocyanin, [61] Chlor [51] Angewandte Chemie Aufsätze e6, [56b] Doxorubicin (Abbildung 5) [62] und Pyropheophorbid [34] [68] So kçnnen PS-XLNP-Komplexe direkt im Tu mor durch den effektiven Energietransfer von den angeregten XLNP zum Photosensibilisator aktiviert werden. Der grçßte Vorteil der Verwendung von Rçntgenstrahlung ist deren Fähigkeit, tief in das Gewebe einzudringen und somit tiefe Tumore behandelbar zu machen.…”