Early detection of SARS-CoV-2 infection is critical to reduce asymptomatic and pre-symptomatic transmission, curb the spread of variants, and maximize treatment efficacy. Low-analytical-sensitivity nasal-swab testing is commonly used for surveillance and symptomatic testing, but the ability of these tests to detect the earliest stages of infection has not been established. In this study, conducted between September 2020 and June 2021 in the greater Los Angeles County, California area, initially-SARS-CoV-2-negative household contacts of individuals diagnosed with COVID-19 prospectively self-collected paired anterior-nares nasal-swab and saliva samples twice daily for viral-load quantification by high-sensitivity RT-qPCR and digital-RT-PCR assays. We captured viral-load profiles from the incidence of infection for seven individuals and compared diagnostic sensitivities between respiratory sites. Among unvaccinated persons, testing saliva with a high-analytical-sensitivity assay detected infection up to 4.5 days before viral loads in nasal swabs reached concentrations detectable by low-analytical-sensitivity nasal-swab tests. For most participants, nasal swabs reached higher peak viral loads than saliva, but were undetectable or at lower loads during the first few days of infection. High-analytical-sensitivity saliva testing was most reliable for earliest detection. Our study illustrates the value of acquiring early (within hours after a negative high-sensitivity test) viral-load profiles to guide the appropriate analytical sensitivity and respiratory site for detecting earliest infections. Such data are challenging to acquire but critical to design optimal testing strategies with emerging variants in the current pandemic and to respond to future viral pandemics.

Paclitaxel (PTX) is one of the most successful drugs ever used in cancer chemotherapy, acting against a variety of cancer types. Formulating PTX with Cremophor EL and ethanol (Taxol®) realized its clinical potential, but the formulation falls short of expectations due to side effects such as peripheral neuropathy, hypotension, and hypersensitivity. Abraxane®, the albumin bound PTX, represents a superior replacement of Taxol® that mitigates the side effects associated with Cremophor EL. While Abraxane® is now considered a gold standard in chemotherapy, its 21% response rate leaves much room for further improvement. The quest for safer and more effective cancer treatments has led to the development of a plethora of innovative PTX formulations, many of which are currently undergoing clinical trials. In this context, we review recent development of PTX drug delivery systems and analyze the design principles underpinning each delivery strategy. We chose several representative examples to highlight the opportunities and challenges of polymeric systems, lipid-based formulations, as well as prodrug strategies.

Transmission of SARS-CoV-2 in community settings often occurs before symptom onset, therefore testing strategies that can reliably detect people in the early phase of infection are urgently needed. Early detection of SARS-CoV-2 infection is especially critical to protect vulnerable populations who require frequent interactions with caretakers. Rapid COVID-19 tests have been proposed as an attractive strategy for surveillance, however a limitation of most rapid tests is their low sensitivity. Low-sensitivity tests are comparable to high sensitivity tests in detecting early infections when two assumptions are met: (1) viral load rises quickly (within hours) after infection and (2) viral load reaches and sustains high levels (>105– 106 RNA copies/mL). However, there are no human data testing these assumptions. In this study, we document a case of presymptomatic household transmission from a healthy young adult to a sibling and a parent. Participants prospectively provided twice-daily saliva samples. Samples were analyzed by RT-qPCR and RT-ddPCR and we measured the complete viral load profiles throughout the course of infection of the sibling and parent. This study provides evidence that in at least some human cases of SARS-CoV-2, viral load rises slowly (over days, not hours) and not to such high levels to be detectable reliably by any low-sensitivity test. Additional viral load profiles from different samples types across a broad demographic must be obtained to describe the early phase of infection and determine which testing strategies will be most effective for identifying SARS-CoV-2 infection before transmission can occur.One sentence summaryIn some human infections, SARS-CoV-2 viral load rises slowly (over days) and remains near the limit of detection of rapid, low-sensitivity tests.

Local chemotherapy is a clinically proven strategy in treating malignant brain tumors. Its benefits, however, are largely limited by the rapid release and clearance of therapeutic agents and the inability to penetrate through tumor tissues. We report here on a supramolecular tubustecan (TT) hydrogel as both a therapeutic and drug carrier that enables long-term, sustained drug release and improved tumor tissue penetration. Covalent linkage of a tissue penetrating cyclic peptide to two camptothecin drug units creates a TT prodrug amphiphile that can associate into tubular supramolecular polymers and subsequently form a well-defined sphereshaped hydrogel after injection into tumor tissues. The hollow nature of the resultant tubular assemblies allows for encapsulation of doxorubicin or curcumin for combination therapy. Our in vitro and in vivo studies reveal that these dual drug-bearing supramolecular hydrogels enhance tumor retention and penetration, serving as a local therapeutic depot for potent tumor regression, inhibition of tumor metastasis and recurrence, and mitigation of the off-target side effects.

Early detection of SARS-CoV-2 infection is critical to reduce asymptomatic and pre-symptomatic spread of COVID-19, curb the spread of viral variants by travelers, and maximize efficacy of therapeutic treatments. We designed a study to evaluate the preferred test sensitivity and sample type (saliva and nasal swab) for detecting early infections of COVID-19. We performed a case-ascertained study to monitor household contacts of individuals recently diagnosed with a SARS-CoV-2 infection. From those individuals, we obtained twice-daily self-collected anterior-nares nasal swabs and saliva samples and quantified SARS-CoV-2 RNA viral loads in those samples using high-sensitivity RT-qPCR and RT-ddPCR assays. We found that SARS-CoV-2 RNA first appears in saliva and then in nasal-swab samples. A high-sensitivity (limit of detection of ~103 copies/mL) RNA test detected SARS-CoV-2 virus in saliva 1.5 to 4.5 days before the viral load in the paired nasal-swab samples exceeded the limit of detection of low-sensitivity tests. It was possible to observe a high (>107-108 copies/mL) viral load in saliva samples while the paired nasal swab was either negative or had low (~103 copies/mL) viral load. Our results indicate that both sampling site and test sensitivity must be considered to ensure early detection of SARS-CoV-2 infection: high-sensitivity tests that use saliva can detect SARS-CoV-2 infection days earlier than low-sensitivity tests that use nasal swabs. Furthermore, early in the infection, low-sensitivity tests that use nasal swabs may miss SARS-CoV-2-positive individuals with very high and potentially infectious viral loads in saliva.