Trigger-responsive engineered-nanocarriers and image-guided theranostics for rheumatoid arthritis.

Rheumatoid Arthritis (RA), one of the leading causes of disability due to progressive autoimmune destruction of synovial joints, affects ∼1% of the global population. Standard therapy helps in reducing inflammation and delaying the progression of RA but is limited by non-responsiveness on long-term use and several side-effects. The conventional nanocarriers (CNCs), to some extent, minimize toxicity associated with free drug administration while improving the therapeutic efficacy. However, the uncontrolled release of the encapsulated drug even at off-targeted organs limits the application of CNCs. To overcome these challenges, trigger-responsive engineered nanocarriers (ENCs) have been recently explored for RA treatment. Unlike CNCs, ENCs enable precise control over on-demand drug release due to endogenous triggers in arthritic paws like pH, enzyme level, oxidative stress, or exogenously applied triggers like near-infrared light, magnetic field, ultrasonic waves, etc. As the trigger is selectively applied to the inflamed joint, it potentially reduces toxicity at off-target locations. Moreover, ENCs have been strategically coupled with imaging probe(s) for simultaneous monitoring of ENCs inside the body and facilitate an 'image-guided-co-trigger' for site-specific action in arthritic paws. In this review, the progress made in recently emerging 'trigger-responsive' and 'image-guided theranostics' ENCs for RA treatment has been explored with emphasis on the design strategies, mechanism, current status, challenges, and translational perspectives.

Nanobubble Liposome Complexes for Diagnostic Imaging and Ultrasound-Triggered Drug Delivery in Cancers: A Theranostic Approach.

The ability of ultrasound contrast agents to enhance the cell membrane permeability in response to an ultrasound pulse has unveiled avenues to facilitate the delivery of a higher intracellular payload at target sites. In light of the above, we report the development of submicron-sized (528.7 ± 31.7 nm) nanobubble-paclitaxel liposome (NB-PTXLp) complexes for ultrasound imaging and ultrasound responsive drug delivery in cancer cells. With a paclitaxel entrapment efficiency of 85.4 ± 4.39%, the 200 nm-sized liposomes tethered efficiently (conjugation efficiency ∼98.7 ± 0.14%) with the nanobubbles to form conjugates. Sonoporation of MiaPaCa-2 cells upon treatment with nanobubbles and ultrasound enhanced cellular permeability, resulting in 2.5-fold higher uptake of liposomes in comparison to only liposome treatment. This manifested into more than 300-fold higher anticancer activity of NB-PTXLps in the presence of ultrasound in MiaPaCa-2, Panc-1, MDA-MB-231, and AW-8507 cell lines, compared to commercial formulation ABRAXANE. Also, the NB-PTXLp conjugates were found to exhibit echogenicity comparable to the commercial ultrasound contrast agent SonoVue. In addition, the developed nanobubbles were found to exhibit more than 1 week echogenic stability as opposed to 6 h stability of the commercially available ultrasound contrast agent SonoVue. Hence, the NB-PTXLps developed herein could prove to be a promising and minimally invasive theranostic platform for cancer treatments in the future.