A Nanostrategy for Efficient Imaging‐Guided Antitumor Therapy through a Stimuli‐Responsive Branched Polymeric Prodrug

Abstract

A stimuli‐responsive polymeric prodrug‐based nanotheranostic system with imaging agents (cyanine5.5 and gadolinium‐chelates) and a therapeutic agent paclitaxel (PTX) is prepared via polymerization and conjugating chemistry. The branched polymeric PTX‐Gd‐based nanoparticles (BP‐PTX‐Gd NPs) demonstrate excellent biocompatibility, and high stability under physiological conditions, but they stimuli‐responsively degrade and release PTX rapidly in a tumor microenvironment. The in vitro behavior of NPs labeled with fluorescent dyes is effectively monitored, and the NPs display high cytotoxicity to 4T1 cells similar to free PTX by impairing the function of microtubules, downregulating anti‐apoptotic protein Bcl‐2, and upregulating the expression of Bax, cleaved caspase‐3, cleaved caspase‐9, cleaved‐PARP, and p53 proteins. Great improvement in magnetic resonance imaging (MRI) is demonstrated by these NPs, and MRI accurately maps the temporal change profile of the tumor volume after injection of NPs and the tumor treatment process is also closely correlated with the T1 values measured from MRI, demonstrating the capability of providing real‐time feedback to the chemotherapeutic treatment effectiveness. The imaging‐guided chemotherapy to the 4T1 tumor in the mice model achieves an excellent anti‐tumor effect. This stimuli‐responsive polymeric nano‐agent opens a new door for efficient breast cancer treatment under the guidance of fluorescence/MRI.

Cyclic Peptide-Gadolinium Nanoparticles for Enhanced Intracellular Delivery

“…Additionally, a stimuli-responsive polymeric prodrug-based nanotheranostic system with imaging agent (cyanine 5.5 and gadolinium-chelate) and a therapeutic agent paclitaxel (PTX) were fabricated. The imaging-guided chemotherapy investigations to the 4T1 tumor in the mice model showed an outstanding anti-tumor effect [15].…”

CTL–doxorubicin (DOX)–gold complex nanoparticles (DOX–AuGCs): from synthesis to enhancement of therapeutic effect on liver cancer model

“…Coupling agent (300 mL), Manufacturer: Shandong Huikang Medical. 68.8-69.8% electronic grade nitric acid; electronic grade hydrochloric acid, Manufacturer: South Korea's DUKSAM company; tuning solution for ICP-MS: 7 Li, 59 CO, 115 In, 238 U, Manufacturer: Thermo, 1.0 mg L À1 ; internal standard solution: 6 Li, 45…”

“…3,4 In this context, nanotechnology-based platforms (as nanocarriers) have emerged as adequate candidates for guiding the drug therapeutic massively and selectively to the tumor, thus limiting the common side effects and pharmacokinetic problems related to standard therapies. 5,6 At the tumor site, specic receptors play a key role in determining such host/guest recognition. Exploiting new potential target sites is therefore of primary importance given the heterogeneity of tumors.…”

Co‐Assembly of Gd(III)‐Based Metallosurfactant and Conjugated Polymer Nanoparticles in Organosilica Cross‐Linked Block Copolymer Micelles for Highly Efficient MRI and Fluorescent Bimodal Imaging

“…However, the synergistic optimization of these two key factors would be beneficial to further boost the relaxivities of the CAs. Moreover, by combining MRI with other imaging modalities, like fluorescence imaging, [ 18 ] it would enable bimodal imaging [ 19 , 20 ] with subcellular resolution and deep tissue penetration.…”