Validation of Dual-Action Chemo-Radio-Labeled Nanocarriers with High Efficacy against Triple-Negative Breast Cancer

Abstract

Identification and selectivity of molecular targets with prolonged action for difficult-to-target cancer such as triple-negative breast cancer (TNBC) represent a persisting challenge in the precision delivery of therapeutics. In the quest to target undruggable sites, this study validates the bioavailability of polydopamine-sealed mesoporous silica nanocarriers (PDA-mSiO 2 ) for in vivo drug delivery to TNBC. For controlled transport and release, the chemotherapeutic drug doxorubicin was encapsulated in mSiO 2 nanocarriers coated with a PDA layer serving as a stimuli-responsive gatekeeper or seal. For unifying targeting and treatment modalities, these nanocarriers were covalently conjugated to a macrocyclic chelator (DOTA) and folate (FA-mSiO 2. ) that enabled incorporation of radionuclides and identification of FR Alpha (FolRα) receptors present on TNBC cells. The robust chemical design of FA-and DOTA-functionalized PDA-coated mSiO 2 nanocarriers constitutes mild reaction conditions to avoid the loss of surface-bound molecules. The radiolabeling studies with the theranostic pair 68 Ga and 177 Lu showed quantitative trends for radiochemical efficacy and purity. Nanocarriers equipped with both radiolabels and affinity ligands were optimally stable when incubated with human serum for up to 120 h ( 177 Lu), demonstrating hydrophilicity with a partition coefficient (log P) of −3.29 ± 0.08. Specifically, when incubated with TNBC cells, the cells received significant FA-mSiO 2 carriers, demonstrating efficient carrier internalization and time-dependent uptake. Moreover, in vivo results visualize the retention of drug-filled carriers at the tumor sites for a long time, which holds promise for therapeutic studies. This research work demonstrates for the first time the successful dual conjugation of nanocarriers through the colocation of radionuclides and anticancer drugs that is promising for both live molecular imaging and enhanced therapeutic effect for TNBC.

Carriers for hydrophobic drug molecules: lipid-coated hollow mesoporous silica particles, and the influence of shape and size on encapsulation efficiency

“…Iron oxide nanocubes were synthesized following a solvothermal reduction pathway published elsewhere. 53,54 Briefly, 0.8 g polyvinylpyrrolidone (PVP) was dissolved completely in 10 mL of N,N-dimethylformamide (DMF). PVP act as a stabilizer to regulate nucleation and growth uniformly across all axes preventing particle aggregation and kinetically controlling the growth of specific facets by binding onto others.…”

“…Iron oxide nanoellipsoids were synthesized using a literature-reported method. 54 In brief, 1.3 g of iron chloride hexahydrate was dissolved in 204 mL of water with stirring until complete dissolution. To this iron chloride solution, ammonium hydrogen phosphate (13.2 mg) was added and stirred for 30 minutes to ensure complete mixing.…”

Biocompatible Hollow Gadolinium Oxide Nanocarriers for the Transport of Bioactive Molecules to Cells

“…Diagnostic imaging is a cornerstone of modern medicine that continues to be the most frequently applied approach for dealing with a broad range of ailments and conditions. − In this direction, previous studies have demonstrated the potential of solid and hollow nanocarriers (5–100 nm) for multimodal imaging using MRI, PET, SPECT, and CT techniques by enabling controlled transport, selective uptake (active targeting), and tracking (fluorophores and dyes) of drug molecules. − The availability of new imaging modalities can fundamentally bring potential changes in how various cells, tissues, and organs can be visualized and treated during specific stages of a particular disease or inflammation. , The use of nanocarriers for disease administrations has shown progress due to their ability to improve drug-delivery efficacy, reduce toxicity, and enhance the specificity of drug accumulation to cells. , The improved cellular responses are linked to the advancement in the physiochemical properties of nanocarriers, bioconjugation strategies, and stimuli-responsive polymeric coatings. , The advanced drug delivery strategies apply specific functional molecules or hydrophilic polymers that offer electrostatic forces, hydrogen bonding, and π–π stacking possibilities to effectively guide and attract therapeutic agents to specific sites within the body, which consequently optimizes the outcome of medical treatments. ,, …”